The Reds welcome their arch rivals to Merseyside with the Premier League summit in their sights, requiring a three-goal win to move joint-top alongside Manchester City.
Mane, a reported target for Manchester United when Louis van Gaal was in charge last year, believes that this latest tussle between the English heavyweights could surpass anything that he has previously competed in.
"Maybe this will be the biggest game I have played in," he told The Telegraph. "My games for Senegal will have been the biggest so far. For my club, I think my biggest was my debut for Southampton against Arsenal. We won and I scored.
"I was under big pressure so for me that was amazing. Now this will be one of the most important. Everyone would like to score in a game like this.
"It's normal the fans and people will think this is a particular type of game. We know it's one of the big games of the season. It might be like El Clasico but, really, when the games starts and you get on to the pitch, then you do have to treat it more like a normal game."
Mane has made a positive start to life at Liverpool, scoring three goals in his first six league games and setting up one goal.