Uruguayan Bentancur has been out since early January with a serious hamstring injury that required surgery.
Spurs are in 18th place with six games remaining, two points behind the safety zone, and in danger of a first relegation from the top flight since 1977.
The return of Bentancur and fellow midfielder Yves Bissouma is welcome news for the club's new boss, De Zerbi, ahead of his first home game in charge, although he confirmed that Argentina international Cristian Romero is out for the season.
"Bentancur is available to play," the Italian told reporters on Friday. "I don't know if he'll start the game or not. Bissouma is available."
Tottenham captain Romero injured his knee in a collision with goalkeeper Antonin Kinsky during the 1-0 defeat at Sunderland last weekend, a result that stretched their winless league run to 14.
"Romero, I'm really sorry for him and his injury," De Zerbi said.
"First of all, non-stop, the people have to know he's suffering because of this injury and because he can't play any more for us in this season.
"He's a great captain for us. We have to be positive, we have Radu Dragusin and Kevin Danso, they are very good to play and give us quality with the ball."
De Zerbi, Spurs' third manager this season, has little time to turn the London club's fortunes around, and said their survival prospects were as much about mentality as ability.
De Zerbi tries to lift spirits
He attempted to raise morale this week by taking the first team out for a meal.
"I have to get to know my players better and better each week," De Zerbi said. "We have no time to lose. I can bring myself, my philosophy of football, but I'm working to create a good atmosphere, a good relationship with the players.
"I think in this moment for Tottenham the qualities of the players are important, but the spirit and the love the players put into their club are more important."
"I don't know if we'll win tomorrow because of (going out) for dinner. The food was amazing.
"But if we win, I'm ready to pay for dinner every week. I believe in human relationships and the spirit and the soul of the players. We need everyone on the pitch to help their teammates and push for one target.
"If we don't achieve our target, everyone loses something in their career."
De Zerbi, whose Brighton career began against Spurs, confirmed that Kinsky would continue in goal with first-choice Guglielmo Vicario still not ready following a hernia operation.