The Tottenham manager is expecting Lazio to be in high spirits after securing a goalless draw with Italian champions Juventus in Turin at the weekend.
But Villas-Boas is optimistic Spurs can get three points against the Biancazzurri and put themselves in pole position to reach the knockout stage in Group J.
“We can be in a very good position if we win this game,” said Villas-Boas.
“We expect a very difficult game. Their last two results have been positive and the influence of the derby against Roma is always very important to their motivation.
“They also drew against Juventus and the league position they hold [fifth] is what they want. You can see why they will be up for it.
“We will be up for it for sure because we don’t want to delay things, if there is a possibility of qualification here, that’s what we’re going to play for. That’s important for the squad.
“It could be a good European night. It’s a game – and I’ve spoken about this in the past – that could be a Champions League fixture, playing in this stadium against a team full of history. I’m sure both teams will approach it in that way.”
“If we manage to win tonight, we will move onto nine points. Lazio take on NK Maribor in their final group match and in that scenario, Lazio would be on eight points and NK Maribor on a maximum of seven (if they win tonight) – therefore, it wouldn’t be possible for both teams to overtake our nine points.”
• The sides drew 0-0 in their first meeting on matchday one, with Hugo Lloris keeping a clean sheet in his first game for Spurs, though his opposite number Federico Marchetti was the busier goalkeeper on the night.
• Spurs’ eight games against Italian teams have ended W3 D3 L2. They famously reached the final of the inaugural Uefa Cup in 1971-72 after beating AC Milan over two legs in the semi-finals.
• Lazio have won five of their last six European home games – including all three this season – with that excellent run broken up by a 3-1 loss to eventual winners Atlético in last season’s round of 32.
• Both of Spurs’ away games in Group J have ended 1-1. Their only win in their last five away trips in this competition was a 4-0 triumph against Irish semi-professional side Shamrock Rovers in last season’s group stage.