The Belgian midfielder is currently suffering a recurrence of a hip injury he had while at Fulham, and the Portuguese manager confirmed his absence for the match between the rivals.
Asked if Dembele would be ready, Villas-Boas replied, "No, not for this game."
"Lennon had a scan [on Wednesday], and it's fine on his hamstring," Villas-Boas said. "We have to wait and see, because I think today is an important day. They had quite a bit of time to rest, to recover, and we have to wait and see if we are able to give them a session for today.
"[Defoe and Lennon] haven't trained with the team yet, they trained separately yesterday, and on the recovery, on a lighter session basically, on their own, individually. We'll have to see today how they return, see if there's any disturbance."
The 35-year-old boss has been left in no doubt as to the importance of the upcoming game to both the club and its fans.
"I've been getting it for the last two weeks to be fair," Villas-Boas explained. "People have been speaking about it quite often in between us - the staff and the chairman - so you understand the importance of it. The voice out from the fans means this is a game where the passion is extremely high and it's a game that represents three points, but it really represents more in the history of North London derbies."