Cam'ron's defending O.J. Simpson's legacy ... saying people need to back off since a jury acquitted him -- and blasting Caitlyn Jenner in the process.

The rapper hopped on the "It Is What It Is" podcast Friday to discuss Simpson's legacy the day after he died, and immediately started defending the controversial figure.

Cam points out a jury found O.J. not guilty of the murders of Nicole Brown Simpson and Ron Goldman in his 1995 criminal trial ... so, he says he's shocked people think it's fine to call him a murderer.

And then, Cam loses his cool a bit ... slamming Caitlyn for writing "Good Riddance" in regards to Simpson's death -- and bringing up her fatal 2015 car accident.

Cam'ron says Cait shouldn't get all high and mighty 'cause she's killed someone ... and even paid a $800,000 settlement because of it.

He also roasts her reasoning for the crash here -- remember back in 2016 she told reporters she was running from paparazzi when the fatal crash happened. Cam'ron says she ain't Princess Diana, and probably didn't need to speed away like she had.

BTW ... CJ already blasted social media users for attacking her on X in this exact same manner -- telling people to remember O.J. essentially bragged he could kill Nicole and get away with it which is way different than her reaction.