Spurs current three-match winning streak means they are favourites in what will be Defoe's 15th appearance in a north London derby.
"It's the big one, a massive game," Defoe said.
"Games like these are the ones you want to play in. I will definitely be ready for it. I'm sure the fans can't wait and we can't either.
"With the way that we are playing, we are confident. If we play like we did against Liverpool, with the same intensity, the same passing and the same movement that we did against them, then I can't see why we can't win the game."