Rangers were beaten 2-0 by Manchester United hours before the Black Cats met Spurs at White Hart Lane, results that leave the two sides two points apart.
"It's unforgiving, so mentality must be the same," O'Neill told BBC Newcastle.
"If there's such a thing as saying this game has the same importance as the Tottenham game, that would be right."
He added: "We saw the efforts that QPR put in against Manchester United, I know they could have conceded a few more goals, but they could have scored two or three themselves.
"They will be battling right until the end."
O'Neill's arrival on Wearside has brought a win and a defeat in his opening two games in charge, following Steve Bruce's departure earlier this month.
Wednesday's game brings the Northern Irishman head-to-head with Neil Warnock and O'Neill said: "I've got much respect for the manager, he's been an excellent manager for a long time now.
"From that viewpoint, you probably know what to expect from his teams and commitment would probably be top of the list."
You can hear the full interview with Martin O'Neill in the build-up to QPR v Sunderland on BBC Newcastle 95.4FM from 1915 GMT on Wednesday, 21 December.