Spurs greatly missed Dembele's calmness and distribution as their four-match winning streak came to an end at the hands of Chelsea, who ran out 4-2 winners at White Hart Lane.
Dembele, who has been a big hit since arriving for £15million on deadline day, had to come off at half-time during Belgium's win over Scotland on Tuesday after the 25-year-old fell and triggered an old hip injury he suffered at Fulham last season.
The versatile player missed three games towards the end of January with the same problem and Villas-Boas admits losing Dembele for a similar length of time would be a big blow for the Londoners.
"Top players are missed," the Spurs boss said.
"He had a scan, but we haven't seen the results yet. He suffers discomfort and pain on his hip which is not something that shows on the scan so it's difficult to assess.
"Fulham took him off for a period of two weeks. He had a chance to play (yesterday) and had a late fitness test but the pain didn't go away.
"It's something that comes back to him. He fell awkwardly in the Scotland game against Belgium and felt the pain."
Without Dembele, and Gareth Bale, who missed the game because his partner went into labour, Spurs looked weak in midfield, with Tom Huddlestone still lacking match sharpness after recovering from a long-term ankle injury this summer.
Much had been made of Villas-Boas' hidden determination to get one over on his old employers and defender Jan Vertonghen admits the manner of yesterday's London derby defeat was frustrating.
Since Villas-Boas arrived at Spurs this summer, the Portuguese has failed to instil a sense of consistency in his team's home performances, although his predecessor Harry Redknapp also struggled to achieve as much last season, particularly towards the end of the campaign.
The victory over Aston Villa aside, Spurs have failed to produce a solid 90-minute display at White Hart Lane this season. Only a much-improved second-half display allowed Spurs to beat QPR and the team were patchy at best against West Brom and Norwich.
And they were terrible in the first half, allowing Gary Cahill to open the scoring during a period in which Chelsea should have sealed the match.
"At home we seem to play better in the second half than the first," said Vertonghen, who signed from Ajax this summer.
"We need to think about how to put two strong halves together.
"We need to work out how to put a bit more pressure on teams from the start.
"They were the best team I faced this year, but I knew they would be.
"I knew their players before I came here and what they are capable of.
"Chelsea are a good team but I feel we should have done better."
Gallas drew Spurs level with his first for the club just after the break and Jermain Defoe netted his 200th career goal moments later, but things started to unravel for the hosts halfway through the second period.
Gallas, whose poor clearance allowed Cahill to score, again failed to clear his lines properly, allowing Juan Mata to score.
The Frenchman then let the Spaniard slip past him so he could convert an Eden Hazard pass to put Chelsea back in front soon after.
Many were surprised that Villas-Boas has started Gallas in every game this year given that he is 35, but Vertonghen insists the Spurs skipper is not past it.
"William is very experienced and with his experience he can be a very good player for us," Vertonghen said.
"He is our captain and an important player.
"He treats me like I am his little brother so that's why he is a very good captain.
"He always wants the best for me, even though we are both centre-backs. I really appreciate him."