It is customary to make a nod to classic encounters between these two clubs in the Premier League era whenever they meet, but they meet in darker moods than usual this weekend.
Newcastle United are only two places above the relegation zone and can still go down in more than just theory. Admittedly, no one has really seen them as realistic candidates for a drop into the Championship all season, but that threat is still there and will haunt the club until it disappears with a win.
Liverpool―who will enter this game at St James' Park in seventh place―have now seen all hope of European football next season pretty much disappear, with the only thing left to play for being the challenge to finish above Everton―something of little consequence outside Merseyside.
Regardless of that, boss Brendan Rodgers will be desperate to deliver a win following what has been yet another trying week in the recent life of Liverpool Football Club, and with the Reds having drawn all three matches they've played so far in April, that need for a win should be apparent.
In the black and white corner, Alan Pardew's Newcastle side will be desperate to put on a show for their home fans after they lost the Tyne-Wear derby with Sunderland 3-0 in their last St. James's Park contest.
Start slowly here, and they are likely to hear the backlash from some of their fans, especially given that they'll be facing a team who'll be without their star striker for well-publicized reasons.
So, both teams enter the game with a lot on their minds...
Three words: Paolo Di Canio.
The Newcastle fans will still be seeing the madcap Italian jumping and sliding his way around St James' Park in their nightmares for months to come―or at least until they play his Sunderland team again―and so their heroes owe them a performance.
The point gained from a 1-1 draw at West Bromwich Albion last time was all well and good, but it hasn''t completely killed off relegation fears just yet, with the Magpies sitting on 37 points along with, but crucially below, both Stoke and Sunderland.
Pardew will be desperate for a result to reach what many call "the magical 40-point mark" in what is his side's penultimate home game of the season, and with a tricky trip to West Ham and a match against Arsenal on the horizon, he'll be desperate to confirm safety as soon as possible.
You may not have heard, but there was actually a football match at Anfield last Sunday.
Liverpool gained a point from it thanks to a 97th minute goal from a player who shouldn't have been on the pitch, but now they're without Luis Suarez the Reds will be looking for another strong performance from a man who impressed after coming off the bench against Chelsea.
This, and indeed the nine domestic games that follow it, gives Daniel Sturridge a chance to prove his worth as Liverpool's central forward, a position in which he has impressed in fits and starts during his brief Reds career.
With a Merseyside derby on the horizon and the prospect of finishing above Everton the only thing that the Reds have to play for the rest of this season, Sturridge will be looking to lead the line impressively in a match he is likely to approach with confidence.
Both men look to lead their teams from midfield, both have a terrific ability to score from long range and both are the men looked to when inspiration is needed.
The midfield is only going to be big enough for one of Yohan Cabaye and Steven Gerrard on Saturday, though, and playing at home it will be the Frenchman who will look to take control of proceedings.
Liverpool have revealed that Steven Gerrard is currently struggling with a shoulder problem that is likely to require surgery in the summer, but the Reds skipper has played in every minute of every one of the Reds' Premier League games this season and is in no rush to throw that record away.
In a match in which control of the midfield is likely to be key―with the likes of Moussa Sissoko and Jordan Henderson sure to be providing energy in that area―it is likely to be the battle between the two star midfield men that shapes the contest.
As usual, it was that man Suarez who hit the headlines the last time these two met at Anfield in November.
Despite dominating for large periods of the game, Liverpool were continually wasteful and fell behind when Cabaye controlled well and finished past the Reds' stand-in goalkeeper Brad Jones.
As they continued to press for an equaliser, Liverpool then grabbed it spectacularly as a long ball forward from Jose Enrique was expertly controlled by Suarez before the Uruguayan waltzed around Tim Krul and tapped the ball into the empty net.
Suarez, Suso, Raheem Sterling, Nuri Sahin and Jonjo Shelvey all came close to a winner for the Reds, but they had to settle for a 1-1 draw despite Newcastle seeing Fabricio Coloccini sent off six minutes from time for a foul on Suarez.
The Magpies are sweating over the fitness of both Papiss Cisse and Cheick Tiote, although both are expected to be passed fit. Davide Santon and Coloccini are still at least a week away from returns, whilst Tim Krul is out for the rest of the season and Hatem Ben Arfa may only be fit enough for a place on the bench.
Likely XI: Rob Elliot, Mathieu Debuchy, Mapou Yanga-Mbiwa, Steven Taylor, Massadio Haidara, Cheick Tiote, Moussa Sissoko, Yohan Cabaye, Jonas Gutierrez, Yoan Gouffran, Papiss Cisse.
The Reds are, of course, without the banned Suarez, and so Sturridge will come in to replace him in what is likely to be the only change to the starting lineup from the draw with Chelsea.
Sterling, Fabio Borini and Martin Kelly have all returned to training following injuries, with first-team coach Mike Marsh revealing that the Italian forward could make the squad for St. James' Park.
Likely XI: Pepe Reina, Glen Johnson, Jamie Carragher, Daniel Agger, Jose Enrique, Lucas, Steven Gerrard, Jordan Henderson, Stewart Downing, Philippe Coutinho, Daniel Sturridge.
Having scored 34 percent of their 88 goals this season, Liverpool's reliance on Suarez is clear to see, but in scoring 29 times away from home in the Premier League this season the Reds are the fourth-highest away goalscorers in the top flight.
Newcastle's seven home defeats this season gives them the third-highest total in the division behind Wigan and Aston Villa―coincidentally the clubs where Liverpool achieved their last two away victories.
Moussa Sissoko is arguably the hosts' key man at home given that he has scored three goals in his five appearances at St. James' Park, whilst Papiss Cisse has scored in five of his last six home appearances―with three of those being stoppage-time winners.
Without Suarez, Liverpool's key hope may be Philippe Coutinho, who has seen his most effective performances for the Reds come away from home.
In four appearances on the road, the Brazilian has been involved in four goals, scoring one and providing the other three.
Stats from WhoScored.com