Jose Mourinho's side travel to St James' Park on Saturday with 11 wins and three draws from their opening 14 matches of the Premier League campaign, and are six points clear at the top of the table.
Their latest victory over Tottenham on Wednesday came without striker Diego Costa, but even his absence did not put Chelsea off their stride as they won 3-0.
Cisse admits Saturday's clash will be Newcastle's biggest game of the season, but remains positive that they can frustrate the league leaders and replicate the 2-0 victory they achieved on home soil last November.
"All the players know this team [Chelsea] is the big one this year," he told the Shields Gazzette. "If you play this team, you need to be clear in your head about your job.
"You need to play well, and maybe you win the game.
"It's a big game. We need to be ready, because Chelsea will give us a very hard game.
"I know the players will be ready for this game.
"Maybe Newcastle will beat them on Saturday!"
Cisse will hope to lead the line against Chelsea having scored his fifth league goal of the season following his half-time introduction against Burnley.
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