Past hosts and winners in traditionally liberal Hollywood often commented on current events, at times sparking angry critiques from Donald Trump on social media.
Republican Trump returned to the White House as president in January.
"I think as host I cannot ignore the moment we're in right now, but also it's threading a needle," O'Brien, a first-time Oscars host, said at a press conference on Wednesday.
"I want to do it with humour and also make sure the night doesn't drift into only about that."
The Oscars will be broadcast live from the Dolby Theatre in Los Angeles.
O'Brien said he had a responsibility to celebrate the actors and craftspeople who worked on the nominated movies while acknowledging current events.
"It's a difficult line to walk, but I'm determined to do it," he said.
He promised a festive night, a luxurious tuxedo custom made for him by a Los Angeles designer and "for the first time in my career - incredible lighting".
He also joked that he would take jabs at beloved Hollywood figures such as Ron Howard and Tom Hanks.
"I'm going to take 'em both down."
O'Brien said he could not reveal much else about the show.
"I don't go to rehearsals. I hang out at a Cheesecake Factory," he quipped.
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