Brendan Rodgers' side goes into the Europa League game 2-0 down on aggregate and missing a host of big names, but the Spanish goalkeeper says the Anfield fans can turn the tie.
Daniel Sturridge and Philippe Coutinho are ineligible for Brendan Rodgers' side while Fabio Borini is likely to miss the rest of the season with a dislocated shoulder, leaving options in forward areas thinly spread.
However, the Reds overcame Swansea at the weekend with an impressive 5-0 victory at home, and the Spanish goalkeeper has called on the famous Anfield crowd to cheer on their side once again.
"We'll be fine, there's no doubt the manager will work on [the formation] and we will produce a team that is capable of winning the game and go through to the next round," he told the club's official website. "As the manager said after the game, the next goal in the tie is going to be vital - and if we can score that goal, with Anfield right behind us, it will be very, very important. We always have great chances at Anfield - five or six chances in front of goal - and this will be no different.
"Two-nil was not what we went [to Zenit] for, but we could have scored two or three goals and it would have been a different story. But it is the way it is and 2-0 is a very tough result to overturn, but if there is one place that can do it, it's Anfield - there is no doubt about that."
Reina hailed the influence his team's supporters can have on the side while it is playing, and says a good atmosphere will be integral to any hopes Liverpool has of success on the night.
"Everybody knows about Anfield on a European night and I can tell you from experience, it's very impressive when you play against Liverpool at Anfield," he added. "The Chelsea second leg in 2007 was a good example. Anfield was rocking that night and I haven't been in an atmosphere like that since.
"It's up to both, players and fans. We have to show character from the beginning, especially in the first 15-20 minutes to get the people right behind us, but then they will lift us in the weak moments as they always do. I am really optimistic. It is a very difficult score to turn around, but with the supporters right behind us I think the mentality will be spot on."