The Portuguese outfit sits third in Group C, three points behind the Greeks, who face a tricky trip to the Parc des Princes to take on 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' side is 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 its Champions League campaign when it beat Anderlecht 2-0 in its first game back in September, but it has only picked up one point from the three games since then.
Still, Benfica comes into the game on the back of a 1-0 win against Braga on Saturday and it is third in the Primeira Liga, just a point behind leaders Porto.
Anderlecht needs to win both of the last two group matches to have any chance of progressing to the knockout stages, and even then that would leave the team reliant on other results going the right way.
The Belgian champions are bottom of the group but claimed a surprise draw at PSG in its last European encounter to get up and running.
John van den Brom's side conceded 10 goals and failed to score in its first three games, including a 5-0 home thrashing against a Zlatan Ibrahimovic-inspired PSG.
Demy de Zeeuw gave Anderlecht a shock lead at the Parc des Princes, but Ibrahimovic denied them a stunning win with an equalizer two minutes later.
The Belgian outfit was beaten 2-1 at Charleroi at the weekend and is down in fifth place in the Pro League.