The Italian giants, who have picked up just five points from four matches and are a point ahead of their hosts, are in danger of not progressing to the second phase of the competition for the first time since the 1999-00 season.
However, Massimiliano Allegri's side will secure qualification for the knockout rounds if they win and Russian champions Zenit St Petersburg fail to beat the already-qualified Malaga in the other Group C fixture on Wednesday.
Anderlecht defeated Zenit 1-0 at home in their last Champions League game and will give themselves a very good chance of making it through to the last 16 with victory over Milan in Brussels.
There are no suspensions for either side.
Possible starting lineups:
Anderlecht: Proto, Gillet, Kouyate, Nuytinck, Safari; Biglia, Kljestan; Bruno, Praet, Jovanovic; Mbokani
Milan: Abbiati, Abate, Mexes, Bonera, Constant; De Jong, Montolivo, Boateng, Emanuelson, El Shaarawy, Pato
Sports Mole says: 1-1