The two sides played out a goalless draw a week ago at Anfield but a more open game can be expected in the cup given the expected rotation.
United came from behind to defeat Fulham at Craven Cottage on Wednesday, with goals from a rejuvenated Paul Pogba and summer signing Edinson Cavani securing all three points.
As a result, the Red Devils sit two points clear at the top of the league – and they’ll be looking to compound more misery on their out-of-form rivals.
Liverpool followed up that drab performance with a home defeat to Burnley, and the Reds are yet to score a league goal in 2021.
Their chances of a win over United in the cup appear to be slim, as the Reds have only reached the fifth round of the FA Cup once under Jurgen Klopp.
They did so last year, but were defeated by Chelsea at that stage.
Here’s everything you need to know about the match:
When is it?
The fixture will kick-off at 5pm GMT at Old Trafford.
How can I watch it?
The match is live on BBC One and BBC One HD, with coverage starting from 4:30pm GMT.
What was the team news?
Dean Henderson and Alex Telles could be handed starts for United, but Ole Gunnar Solskjaer will still field a strong team – so Bruno Fernandes, Harry Maguire and Edinson Cavani are all in line to play once more.
Mohamed Salah and Roberto Firmino are set to return to the starting line-up while Sadio Mane will be rested, but Jordan Henderson could miss out with a muscle injury. Diogo Jota and Naby Keita are out.
Manchester United: Henderson; Wan-Bissaka, Lindelof, Maguire, Shaw; McTominay, Pogba; Greenwood, Van de Beek, Rashford; Cavani
Liverpool: Alisson, Alexander-Arnold, R. Williams, Fabinho, Robertson; Thiago, Wijnaldum, Milner; Jones, Salah, Firmino
Manchester United: 8/5
Liverpool are criminally out of form, particularly after the home loss to Burnley, while Manchester United continue to grind out favourable results. Both sides will go for the win in a game that could define their seasons, for better and worse, but I think the home side will prevail. Manchester United 1-0 Liverpool.