Lazio are top of the group and a draw for Spurs in Rome and then a win in the final game against Greek side Panathinaikos would be good enough for Villas-Boas' men too.
But Villas-Boas - who won the tournament two years ago with Porto - does not want to leave it until the final match.
"It's all about this game," said Villas-Boas. "It will be important for us to win and qualify. It will give the squad an important feeling of beating a great team away from home."
Paul Gascoigne, a hero to both sets of fans, will be guest of honour at the match.
Gascoigne became a cult hero at Spurs after four successful years at White Hart Lane and he then went on to achieve similar status at Lazio after moving to the Italian capital in 1992.
Gascoigne will defy his fear of flying to make the game, when he is expected to be paraded on the pitch where he won a place in the Biancocelesti fans' hearts by scoring a late winner in the Rome derby during his first season at the club.
Spurs defender Steven Caulker is a big admirer of 'Gazza'.
He said: "He is a Spurs and England legend. He was a fantastic footballer. As a football fan, him coming to the game is extremely special and there are a lot of footballers here who want to be just as good as he was."