"It's time for me to hang up Scully's hat. It just is," Anderson, 49, said Wednesday at the Television Critics Association's winter press tour, according to The Hollywood Reporter. "I'm finished, and that's the end of that."
But does that mean it's the end for the revived series? Not necessarily.
Co-star David Duchovny, who plays Agent Fox Mulder, didn't shut the door on more episodes without Anderson, saying he was "good either way."
"I've tried to say goodbye to Fox Mulder many times and I failed. And they all went and did the show without me, so how do you like that?" Duchovny, 57, joked. "I'm feeling pretty pissed off, now that I remember."
Duchovny left the show as a full-time cast member after its seventh season, but appeared occasionally on the show in the eighth season and briefly in the ninth season, before returning full-time for the latest revival.
But earlier this month, "X-Files" creator Chris Carter said without Anderson, he wouldn't be interested in doing more shows.
“For me, 'The X-Files' is Mulder and Scully. I think if it were without Scully, I wouldn’t do it," he told Collider. "That’s not my 'X-Files.'”
"The X-Files" originally ran from 1993 to 2002. The series also spawned two theatrically released movies.