Inter, currently without a manager following the sacking of Frank de Boer just two days before their trip to England, have one point fewer than Southampton but have inflicted the Saints' only defeat in the competition so far this season.
"It's a crucial game," said Hojbjerg, whose team's last appearance in the tournament came in 2003-04.
"If we win this game I think it looks very good ahead of the knockout stages. If we lose the game, we suddenly can be one step behind, and with only two games left then there is a lot to catch and that can be difficult.
"So it's really important to get a good start to the game, to get a good feeling and atmosphere. The fans have to be there, and I really look forward to it."
Hojbjerg, who joined Southampton from Bayern Munich in the close season, pointed out how the fans had spurred the team on during their narrow 1-0 defeat by Inter at the San Siro last month.
"I must say, I have been at some clubs and I think I have never experienced something like that, and to be that loud doesn't happen a lot," he told the club website. (www.southamptonfc.com)
"The players can feel it, and the players will try to put all their energy into the game... and we will maybe make history and go through to the knockout stages."
(Reporting by Simon Jennings in Bengaluru; Editing by John O'Brien)
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