The Red Devils, sitting in seventh place, harbour an 11-point deficit on fourth-placed Arsenal with 10 games to go this season.
The Gunners' run-in includes games against Tottenham, Chelsea and City, as well as a number of sides scrapping for survival.
This could open the door for United to sneak into the top four, who know that victory over Liverpool will set the side back on their way towards the top spots.
However, the Reds have been in excellent form this season, and they will be hoping that Luis Suarez, Daniel Sturridge and Raheem Sterling can fire the side to glory at Old Trafford.
Liverpool's Australia and New Zealand account tweeted about what could be a big day for strikers at Old Trafford:
A tough test in store for both sides, so let's take a look at what is making the big headlines ahead of the big kick-off in Manchester, with plenty on the line for both sides.
Rooney Hopes For Victory In Big Week
Wayne Rooney knows that only a win will do against Liverpool, as the side prepare for the biggest seven days of their season.
The England striker, who recently committed his future to the club in a long-term deal, will be hoping to fire United to glory over their arch rivals—and against his boyhood rivals, after growing up as an Evertonian.
Speaking exclusively with the Mirror's Simon Mullock, Rooney noted that victory over the Reds is a high priority:
For me, beating Liverpool is always special because of who I am and where I come from, but for a club like Manchester United it can’t be just about stopping Liverpool. We want to win because of what it means to us. This is a massive period.
We still haven’t given up on fourth place and we also think the tie against Olympiakos is retrievable. But we have to be realistic. We have to beat Liverpool because we are running out of games, and if they get a result against us then the gap would probably be too big.
Rooney will also be hoping that victory for United can ease the pressure on manager David Moyes, who oversaw the striker's development at Goodison Park.
The 28-year-old stated that his stay at Old Trafford was largely thanks to the Scot, and he admitted that the manager was happy to dish out a few home truths:
David Moyes’ influence on me signing the new contract was absolutely massive. Certain issues did arise last season that I wasn’t happy about. When David Moyes took over he made it clear to me straight away that he wanted to draw a line under last season. And the key thing was when he assured me that he had total belief in me.
Just as important, he also told me things that I probably didn’t want to hear. He told me I had lost something from my game and that I needed to get back to basics. The boss reminded me about the player I was. He wanted to know what had happened to all my aggression. He said that I’d lost something important from my game – and he wanted it back.
It's a long-term rebuild at Old Trafford and with Moyes' input positive according to Rooney, pressure on the manager may be eased.
However, it's a results business and unless the side can pick up their fortunes and mount a real challenge up the league in the remaining 10 matches, Moyes' first year in the job could become his last.
But by stamping his authority on the club, you've got to think that he has just the right mentality to arrest the club's current fortunes and build on Sir Alex Ferguson's long tenure.
Fellaini Backs United's Attack To Succeed
Midfielder Marouane Fellaini has backed the Red Devils' quality in attack to help the side to victory over Liverpool.
The Belgian midfielder believes that the side have excellent chemistry, and that an abundance of experience can help the side to overcome their Merseyside opponents, according to BBC Sport:
We have a lot of quality in attack - Juan Mata, Wayne Rooney, Adnan Januzaj and Robin van Persie. They give a lot of solutions in attacking positions so that's great that they have that understanding.
Fellaini also stated that the 3-0 win over West Brom last time out, his sixth start of the season, according to WhoScored.com, proved as a big confidence boost to United and highlighted the need to make home advantage count:
When you win, everyone is always happy and we have to keep going like this. It was good for our confidence. We have done well away from home but we need to win at Old Trafford. It's important for our supporters.
The midfielder knows only too well of Liverpool's ability to win in big derbies, after his stint at Everton where the Toffees picked up just one win in 10 opportunities against the Reds.
However, with confidence brewing at the Theatre of Dreams, Fellaini will be hoping to arrest that sorry run and make it two wins against Brendan Rodgers' side as he continues to show why he should be involved within his national set-up at the World Cup.
According to BBC Sport, United will welcome back Rafael after the right-back picked up a knock to his ankle during the win at West Brom.
A return for the full-back will come as a boost to Moyes' men, with the player's ability both defensively and on the overlap allow United to implement their preferred system, with Evra performing a similar role on the left flank.
There could be a return for Nani, too, as the winger has recovered from a hamstring problem and looks in contention to feature.
Meanwhile, Jonny Evans could return to the starting line-up as Javier Hernandez recovers, however, the Mexican striker could once again have to settle for a place on the bench—a customary position for him under Moyes.