The comedian hit the stage during Katt Williams' latest stop -- remember, she's currently touring with him as one of the accompanying acts -- and she went on an absolute tirade against O and TP that was profanity-laden and full of insults, calling them "coon motherf*****s."

Before she got to that though ... she shouted, "F*** YOU OPRAH WINFREY, F*** YOU TYLER PERRY!!!" She also got the crowd to repeat this too, with a crude call-back.

While some audience members piled on, others seemed hesitant to go along ... prompting Mo'Nique to call out an Oprah fan in the audience. She even encouraged the male attendee to bring O "back to Black" by having sex with her.

As the comedian continues on her rant, she facetiously declares her love for Oprah ... but proceeds to call her "simple-minded" and a "raggedy bitch" moments later.

Amid her jarring remarks, Mo'Nique states she will not apologize for anything said during the set ... proceeding to question Oprah's relationship with Gayle King -- suggesting they are romantically involved. Yeah, she goes there ... and it's as shocking as it sounds.

Mo'Nique continues ... "I'm too motherf***ing old to be scared of this bitch. I'm too old to be intimidated by this bitch. I'm too old to hold the motherf***ing truth."

Mo'Nique's longtime feud with OW and TP stems from her allegations they "blackballed" her in Hollywood -- this after Mo'Nique refused to do certain press events for the 2009 film, "Precious," which they produced.

The comedian has bashed Oprah and Tyler on a number of occasions over the years, repeatedly accusing the 2 stars of trying to torpedo her career ... a drum she's been beating repeatedly, and at every opportunity available.

Most recently, Mo'Nique appeared on Shannon Sharpe's "Club Shay Shay" podcast, where she claimed to have a recording of TP admitting to bad-mouthing her -- something Tyler has vehemently denied. This feud's 15 years and counting ... and it's still going strong, even now.