The first leg of this last eight clash at the Constant Vanden Stock Stadium represents a first meeting between the sides for 17 years and could prove crucial ahead of next week's Old Trafford return.
After a second placed league finish last term, Rene Weiler's side missed out on Champions League qualification at the expense of our last 16 opponents FC Rostov.
Having dropped into the Europa League, the Belgian side finished runners up in their group, behind Saint-Etienne (who we beat in the last 32).
They impressively got past Zenit Saint Petersburg in the first knockout round on away goals before a 2-0 aggregate win over Cypriot side APOEL Nicosia set up this quarter-final.
Wayne Rooney has not travelled despite training with the rest of the squad on Wednesday.
Antonio Valencia has not featured in the Reds last two matches but is expected to return here.
Chris Smalling, Phil Jones and Juan Mata are all sidelined with long term injuries whilst Ander Herrera and Eric Bailly are one booking away from a European ban.
David de Gea has recovered from his "minor" hip problem but Sergio Romero could keep his place after a ninth clean sheet of the season at Sunderland.
Anderlecht's top scorer Lukasz Teodorcyzk is doubtful with the 25-goal striker struggling with a shoulder problem.
United boss Jose is looking to be in a strong position ahead of next week's second leg, and said: "Anderlecht are a good team, they play well, press well and have many talented players so it will be difficult.
"We have that second leg as a protection, but we need to put ourselves in a good position.
"If we don't play well we are in a difficult situation, when a team arrives at this stage of a competition, everyone feels they can win it.
"The motivation is high and we are going to give everything, both in the league and in Europe."
United head into the match on the back of a 21-match unbeaten domestic run, whilst Anderlecht hold a two-point lead at the top of the Belgian league.
The other three quarter-final ties take place tonight, as Ajax host Schalke, Genk travel to Celta Vigo and tournament favourites Lyon face Besiktas.
Form guide: Anderlecht D W W W W D United L W W D D W
Match odds: 20/4 Draw 12/5 United 11/3
Referee: Felix Brych (Germany)
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