The Portuguese outfit sit third in Group C, three points behind the Greeks, who face a tricky trip to Parc des Princes to take on already-qualified Paris Saint-Germain
The Portuguese giants are three points behind second-placed Olympiakos with two matches remaining in Group C, after being beaten 1-0 by the Greek champions last time out.
Jorge Jesus's side are six points adrift of leaders Paris Saint-Germain, who only need a point to secure their place in the knockout stage when they host Olympiakos on Wednesday.
Jesus is currently serving a 30-day domestic suspension after an on-pitch altercation with police after his side's victory at Vitoria Guimaeres in September. However, that ban does not apply to European competition so the Benfica coach will be on the touchline at the Constant Vanden Stock Stadium.
The Lisbon outfit made a great start to their Champions League campaign when they beat Anderlecht 2-0 in their first game back in September but they have only picked up one point from the three games since then. Still, Benfica come into the game on the back of a 1-0 win over Braga on Saturday and they are third in the Primeira Liga, just a point behind leaders Porto.
Anderlecht need to win both of the last two group games to have any chance of progressing to the knockout stages and, even then, it would leave them reliant on other results going their way.
The Belgian champions are bottom of the group but claimed a surprise draw at PSG in their last European encounter to get up and running. John van den Brom's side conceded 10 goals and failed to score in their first three games, including a 5-0 home thrashing against a Zlatan Ibrahimovic-inspired French side.
Demy de Zeeuw gave Anderlecht a shock lead at Parc des Princes but Ibrahimovic denied them a stunning win with an equaliser two minutes later.
The Belgian outfit were beaten 2-1 at Charleroi last time out and are down in fifth place in the Pro League.