The Russian side hold a 2-0 lead heading into the second leg of their last-32 tie with the Reds at Anfield.
Liverpool - five times the continent's champions - hope to recreate the atmosphere from some of their most famous European nights to pull them through and Spalletti has warned his players not to sit back.
The former Roma boss said: "We have to play the game as if it was 0-0 in the first game. We have to forget about the 2-0 scoreline.
"We will have to control the match better and not pass the initiative to Liverpool too much.
"We need to be particularly prepared - Liverpool have a very good reputation for scoring in serious matches.
"Often having lost the first leg they have overcome the obstacle and gone on to win.
"Liverpool may push us back but we are going to follow the same tactics and strategy as last week."
Zenit found themselves in the Europa League after being edged out of a Champions League group featuring Malaga and AC Milan.
Milan finished just a point ahead of the Russians but Spalletti was not wondering what might have been as he prepared to watch the Italian giants face Barcelona in a mouth-watering Champions League clash on TV.
The 53-year-old said: "Of course I will watch it, it will be a fantastic spectacle.
"We don't wallow in self-pity. We are not going to feel bitter, we will learn a lesson from it.
"The team's experience is growing at this level. We have played quite a few matches in the Europa and Champions League.
"The players want to carry on gaining more experience and winning games."
Liverpool manager Brendan Rodgers, meanwhile, believes his team have made good progress this season despite acknowledging setbacks along the way.
The Reds' recent form in the Barclays Premier League has been positive - illustrated by a 5-0 hammering of Swansea on Sunday - but Rodgers' first campaign at Anfield has generally been one of inconsistency and frustration.
Tempering the recent run of good results has been a shock loss to League One Oldham in the FA Cup, a disappointing reverse at home to West Brom and defeat at Zenit last Thursday.
That loss in Russia has left the Merseysiders facing an uphill struggle at Anfield Thursday, but Rodgers believes that deficit can be overcome - an achievement which would further his side's development.
He said: "The development of the group since I came in - it was never going to be a bolt of lightning. It was never going to be immediate, sudden impact.
"It was going to be over a little period.
"What I have learned from the group is that process of learning has taken place.
"We have obviously shot ourselves in the foot a number of times but it doesn't mean there hasn't been development.
"We are making progress and this would certainly help that appetite going forward.
"We will put everything into the game to win and get through. If we can do that it would be a great tonic for us."
Rodgers has often been frustrated by his side's inability to score when dominating teams this season, the prolific Luis Suarez mostly excepted.
That situation has started to change following the signing of Daniel Sturridge last month, with the former Chelsea man both in good form and facilitating a change of approach.
But Sturridge will be missing against Zenit as he is not eligible for the competition and, with Fabio Borini injured, Suarez will carry the burden of the attack.