The Russian Premier League leaders were beaten 2-1 in the first leg of their last eight tie in Seville as Carlos Bacca and Denis Suarez scored after Aleksandr Ryazantsev's opener.
Villas-Boas was without the banned quartet of Domenico Criscito, Igor Smolnikov, Danny and Hulk, while Anatoliy Tymoshchuk was only fit enough for a brief appearance off the bench.
That suspended quartet are back in the frame for Thursday's second leg, with Ezequiel Garay and Ryazantsev the only players banned for Zenit.
Viktor Fayzulin is unlikely to feature due to a knee injury.
However, Zenit fans will be buoyed by victories in their last three European home games - without conceding a goal - and Villas-Boas wants to make it a difficult night at the Petrovsky Stadium for Unai Emery's men.
Asked whether the return of numerous players made the task easier, Villas-Boas said: "No it's definitely not going to be simpler.
"Yes they are returning, but what can really help us is support in the stadium.
"I am calling on everyone to come to the Petrovsky and give everything they have for the game.
"The atmosphere that the fans are going to create can really help the team out."
Defending champions and three-time winners Sevilla have won the tournament every time they have made the last eight.
Emery's side have tasted defeat just once in 13 games - the Supercopa Euroamericana loss to River Plate - with their only injury concern being Daniel Carrico (thigh).
Colombian striker Bacca is eager to finish the job in Russia and return to former club and fellow quarter-finalists Club Brugge on the way to the final.
"With Sevilla having it won three times, there is a lot of excitement about playing in it," Bacca told UEFA.com.
"But we don't want to just play in it - we want to become champions. It's not easy, we know that, but the Europa League is a competition that Sevilla and the Sevilla fans like a lot.
"Hopefully we'll get past Zenit and Club Brugge will get to the next round, too, and then we'd face them sooner or later.
"I would like to go back to the Jan Breydelstadion and feel the affection of the Club Brugge fans and win. It would be something special to face them."
‘He instantly popped into our ratings as one of the best U21 midfielders in Europe. The impressive thing is Slot has made him into more of a no.6' Inside Ryan Gravenberch's transformation at Liverpool
‘I don’t think Liverpool would look at Ollie Watkins, a striker isn’t a pressing issue for them – it’s Arsenal who need one’ Former Reds star explains why his old club don’t need an out-and-out forward this summer
