Dembele, 31, has been linked with Inter Milan and a move to the Chinese Super League, with less than 12 months remaining on his contract with the north London outfit.
Spurs have been linked with a whole host of central midfielders as the Belgium international's replacement, but the former Fulham star remains at Tottenham despite doubts over his future.
Berbatov believes keeping Dembele is key because he is the link between attack and defence, despite the club boasting the likes of Eric Dier, Victor Wanyama and Harry Winks in the middle of the park.
"In Tottenham's case it's not who they're signing it's who they need to hold on to," Berbatov said. "For me they obviously need to keep Harry Kane, Alli and Christian Eriksen; they are the triangle of players that cause the most danger and trouble for opposing teams.
"Overall Spurs are strong in every position, but to make it work they also need to keep Mousa Dembele as he is the link between defence and attack."
Dembele turned out 39 times in all competitions this season, before helping Belgium finish above England with a third-place play-off win in Russia. It remains to be seen if he will renew his £80k-a-week contract (Daily Star).
Berbatov turned out 102 times for Spurs during his two-year spell between 2006 and 2008, scoring 46 goals and creating 24, before moving to Manchester United.