Manchester's Reds are going for championship number 19 - a record fourth consecutive league triumph - while the men from the other end of the East Lancs road are in a desperate tussle for fourth place.
But while there's no chance of a trophy at the end of the league campaign for Liverpool, they'll be fired up to try and put the skids on United's attempts to overtake them as the outright most successful team in English football.
The motivation for Sir Alex's troops is clear, with an added incentive of owing Rafael Benitez's side one after three straight defeats to Liverpool.
So, the question is - how would you like to see us approach the game? All out attack playing 4-4-2, Wayne Rooney and Dimitar Berbatov leading the charge? Or perhaps Rooney as the lone forward, behind him a dominating five-man midfield?
You can join the debate on Talking Reds by simply following the format below. Here are some of the best responses we've had so far:
Team & formation: (4-3-3) Van der Sar; Rafael, Ferdinand, Evans, Evra; Carrick, Scholes, Fletcher; Park, Rooney, Nani.
Approach: Counter-attacking, but make sure we keep plenty of possession.
Team talk: No room for mistakes, let's go for the win.
Prediction: 4-1 to United
Posted by: Simon Mureithi
Team & formation: (4-5-1) Van der Sar; Neville, Ferdinand, Vidic, Evra; Valencia, Fletcher, Scholes, Park, Nani; Rooney.
Approach: 4-5-1 works so well against the bigger teams. Park was fantastic against Milan in central midfield so I'd keep him there. We'd have a solid back four and midfield to stop them attacking.
Team talk: Just remember how we felt last season when they beat us, now put that result right!