The Reds will be favourites to progress after seeing off Premier League champions Manchester City in the last round, and they will hope an electric atmosphere at Anfield can inspire the team to a first-leg win.
However, they face a team that knocked out the mighty Barcelona in the quarter-finals despite losing the first leg 4-1 at the Camp Nou.
Here's a look at how you can watch the game, followed by a preview.
Date: Tuesday, April 24
Time: 7:45 p.m. GMT/2:45 p.m. ET
Venue: Anfield, Liverpool
TV Info: BT Sports 2 (UK), Fox Sports 1 (U.S.)
Super Salah Faces Former Team
Mohamed Salah has enjoyed a stunning first season at Liverpool since joining from Roma in summer 2017 and will be out to torment his former side.
The Egyptian has scored in his last six games in a row, with his goal against West Bromwich Albion on Saturday equalling a Premier League record:
Salah also has eight goals in 10 Champions League appearances, so Liverpool will look to use his pace and ability on the ball to hurt Roma.
Defender Kostas Manolas has said his team have no tactics to deal with Salah specifically, but they are confident they can handle him "because we stopped Barcelona and Leo Messi with teamwork," per Joe Rimmer at the Liverpool Echo.
Salah and Roma have already revealed the respect they have for each other on Twitter:
Roma will know all about Salah and the threat he possesses, but stopping him is another matter entirely. On present form, he looks like scoring every time he steps on to the pitch, and it would be little surprise to see him add to his tally on Tuesday night.
Roma Eyeing Another Upset
Roma have already upset the odds more than once in this season's European campaign. Eusebio Di Francesco's side emerged from a tight Group C as winners as they pipped Chelsea to top spot. Atletico Madrid could only finish third and were knocked out of the competition altogether.
Their home form is formidable, as they are yet to lose or even concede a goal at the Stadio Olimpico. However, it's a different story away from home.
While they drew at Chelsea, they were beaten at Atletico, Shakhtar Donetsk and Barcelona. If they can escape from Anfield with a decent result, they will have confidence they can do the business back in Rome.
In Edin Dzeko, they have a striker who has knowledge of English football due to his time with Manchester City, and he has six goals in 10 Champions League outings.
Question marks remain about a Liverpool defence that has shown vulnerability this season, and they conceded two late goals against West Brom on Saturday.
Simon Johnson at the Evening Standard said Dzeko might have enjoyed watching the end of that game:
The two sides have met before, with Liverpool beating Roma in the 1984 European Cup final. Carlo Ancelotti, who played for Roma, said this is a good opportunity for revenge, as shown by Goal:
Roma have shown great team spirit in the competition this season, and that will be needed at what is bound to be a raucous atmosphere at Anfield. The team have shown this season they are no pushovers and, having beaten Barcelona, will feel anything is now possible.