Pep Guardiola's side travel to the Tottenham Hotspur Stadium after Spurs' long-delayed debut in the gleaming 62,000-capacity facility came with a 2-0 win over Crystal Palace.
A memorable atmosphere is anticipated for City's first-leg visit to north London but De Bruyne is more concerned about the quality players such as Harry Kane, Christian Eriksen and Dele Alli bring to the Tottenham ranks.
"I don't care about the stadium," he said. "I care about the team we play.
"Everybody talks about the stadium like it’s something special. Everybody has a stadium. Everybody has supporters. They’ll be up for it.
"I don’t think there will be any difference. They'll probably be a little bit more excited but in the end it's a stadium with supporters.
"If they go to Wembley with 80,000 or there with 62,000, it's going to be the same. It'll be a tough game but I think we'll be alright."
Guardiola thinks City completing an unprecedented quadruple remains "almost impossible" and De Bruyne feels the gruelling schedule they have to negotiate should be acknowledged.
"There's no point thinking about it. Do you know how heavy the schedule is?" De Bruyne said.
"I think people underestimate how the fixtures come that quickly. You can’t think about it. We don't even have time to have a rest ourselves so how can we think about what's going to happen in four weeks?
"We're just going to play Tuesday and then hopefully play a good game."
City fell at the quarter-final stage of the Champions League last season, when they lost 5-1 to Liverpool on aggregate.
They were ultimately unable to recover from a falling 3-0 down inside 31 minutes of the first leg at Anfield.
Ahead of another trip to face a fired-up Premier League rival, De Bruyne was unequivocal over what lessons City can learn from that Merseyside ordeal.
"Nothing," he added. "Different team, different year, different players.
"Last year we had a great season, we didn’t make it beyond the quarter-finals and that's it."