If the Greek champions cannot secure all three points, then Benfica would have to beat Group C leaders Paris Saint-Germain to deny Olympiacos a place in the last 16.
Kostas Mitroglou will be hopeful of increasing his goal tally in Europe this season against the Belgian side, having scored a hat-trick when they met earlier in the campaign.
Anderlecht have only pride to play for, having lost four of their five group stage matches so far, clinching their only point against PSG.
Goals have been hard to come by for the visitors in the Champions League this season, as they have found the back of the net just three times.
Possible starting lineups
Olympiacos: Gago, Siovas, Manolas, Papadopoulos, Weiss, Samaris, Fuster, Holebas, Campbell, Mitroglou, Saviola
Anderlecht: Proto, Deschacht, Mbemba, Borre, Nuytinck, N'Sakala, Praet, Gillet, Milivojevic, Mitrovic, Acheampong
Sports Mole says: 3-1