Wolfsburg beat Inter 3-1 in Germany last week, leaving the Italians with a massive task to overturn the result and reach the quarter-finals of the competition.
“There is hope and we must try,” Mancini told the Italian press. “We need to win by 2-0 and it’s possible to do so.
“It would be fantastic although we know we are facing a very strong side.
“We really want to give our fans some joy and we need a special night where we make things happen.”
Inter have won just one of their last five home games against German sides and will need to show a vast improvement if they are to progress to the last eight of the competition.
The Nerazzurri head into the contest on the back of Sunday’s 1-1 draw against relegation-strugglers Cesena that dropped them to eighth place in Serie A and extended their winless run to four games in all competitions.
“We have to put in a great performance to go through to the next round,” Mancini said. “Wolfsburg are a good team, it’s no surprise they are second in the Bundesliga.
“We will also need a bit of luck and avoid making mistakes.
“We cannot obsess about scoring goals, my players just have to think about giving their best.”
Wolfsburg have won 16 and lost just one of their last 21 games in all competitions.
The Wolves are unbeaten in their last three European away games and warmed up for the encounter in Italy with Saturday’s 3-0 triumph over Freiburg.
“We have to stay focused now because if you don’t then it can become dangerous,” Wolves defender Timm Klose told the Bundesliga website. “We simply have to keep working hard.
“I’m really looking forward to playing against Inter Milan and it’s going to be a great game.
“We want to progress, but we still have some work to do.”
Klose will replace Brazilian defender Naldo, who is suspended on Thursday.
Wolfsburg, coached by Dieter Hecking, are also without midfielder Aaron Hunt, who is out with a knee injury.