"People die over this issue. It's not a joke," Jenner says, schooling the host.
In a preview clip from Thursday's interview, the transgender reality TV star gets into a heated conversation with the host after he asks how her "physique" now compares to what it was like pre-transition. "Obviously, certain areas we know," he said, before she cut him off.
"See you made a comment there and that's why you would get in trouble," she said. "You just said, 'Oh certain areas.' That, to a trans person, is disrespectful."
Morgan didn't understand why what he had said was offensive.
"Because you don't make a joke about that," she shot back. When he once again asked why, she added, "because it's not funny, it's life. And it’s a part of my life and it's a very serious part of my life."
Morgan then asked, "Right, but can't life be funny?", but she wasn't having it.
"I don't take it and I take that very seriously. And so, out of respect to myself and the community, it's not something that you joke about," she continued. "It's something, as I said before, this is serious stuff. People die over this issue. It's not a joke."
Piers said the conversation was "genuinely educational," which Jenner said was her goal when agreeing to appear on the show.
Morgan's "Life Stories: Caitlyn Jenner" episode airs on Thursday at 9pm on ITV.