The two teams are set to face off three months after October's meeting in the League Cup, a game in which the Hammers run out 3-2 victors.
With Kane in arguably the form of his life, having raked in 18 league goals so far to lead the top scorers' chat, Ayew is not any way lost on what they are up against.
"We know Spurs have real quality, but we can stop them again," the deputy Ghana captain told his club's official website.
"Harry Kane has been top class and has done great for his club and country, scoring more than 50 goals in 2017.
"He has got players around him who are giving him great service, too, and he’s been banging in the goals. He’s a top, top striker.
"It’s not easy to deal with him, or with the likes of [Christian] Eriksen, Son [Heung-Min], Alli and their other attacking players, but we’ve done it before, beating them 1-0 at home last season, so why can’t we do it again?
"They are great players who have been playing together for a while, so they know how to play football and they try to go forward.
"That’s Tottenham and we know that they will always play good football, so we have to try to stop that and also play our own game and make them defend too.
"It’s a derby, so I expect there will be chances at both ends, but it’s going to be tough."
In October's thriller, Ayew netted a second-half double to ensure a dramatic comeback win.
"Thursday’s game with Tottenham is a derby and it’s a game that, when you get the opportunity to score and win, you are very, very happy at the end of it," said, the 28-year-old.
"If I can get more goals, like the two I got against them in the Carabao Cup, that would be good, but it’s more important for us to get points.
"It’s going to be a very difficult game, as we know what Spurs are capable of doing and we know their qualities, so we need to stay strong."
Ayew has 16 league appearances, involving nine starts and three goals, to his name thus far this campaign.