Rooney's missed four games with an ankle injury but trained yesterday and could be named on the bench.
Despite Leander Dendoncker's late goal in Belgium that levelled the scores, Henrikh Mkhitaryan's away goal sees the Reds hold a slender advantage with a last-four spot at stake.
Sergio Romero will start in goal - his eighth starts in eleven European fixtures - and Zlatan Ibrahimovic could also return having been rested against Chelsea.
Juan Mata, Chris Smalling and Phil Jones are out for the rest of the season but United have no fresh injuries.
Having won every home match in this season's competition, boss Jose admitted "motivation is high" as the Reds look to reach a first European semi-final since 2011.
He said: "If you don't concede, you go through and that's important.
"We know that they have to score or they are out, we play at home and have won every match here in Europe so far so we do not play for a 0-0.
"When you start this competition, perhaps the desire is not high but at this stage, three matches from the final, the motivation is stronger.
"We showed in Brussels and against Chelsea that we are a good side, but we have to keep our motivation high, that is the most important thing."
Both United and their visitors secured important league victories at the weekend, with United's best performance of the season in our 2-0 win over Chelsea to keep alive hopes of a top-four finish.
Anderlecht, meanwhile, kept their title challenge on course with a narrow win at KV Oostende with captain Sofiane Hanni hitting the winner.
United have reached the last four of this competition once before, under its previous guise of the Inter-Cities Fairs Cup in 1964/65.
We were eventually beaten 2-1 by Ferencvaros in a play-off but that remains the Reds best run in the tournament - the distinctive silverware on offer this time is the only major trophy missing from United's collection.
There seems a sense of fate in United's destiny with the final to be played in Stockholm on May 24 in Zlatan's home city of Stockholm - where a statue will be erected in his honour.
In the other last eight ties, Ajax are in command against Schalke and lead 2-0 while Lyon (2-1) and Celta Vigo (3-2) hold narrow leads over Besiktas and Genk respectively.
The draw for the semi finals will be held in Switzerland tomorrow.
Form guide: United W D D W D W Anderlecht W D D W W W
Match odds: United 1/4 Draw 5/1 Anderlecht 11/1
Referee: Alberto Mallenco (Spain)