Christina Applegate explains 19-year 'SNL' absence in promo - watch
The Up All Night actress is joined in the clip by Jason Sudeikis, who rejects her claim to being "America's sweetheart".
Applegate last hosted Saturday Night Live more than 19 years ago on May 8, 1993, when Adam Sandler, Mike Myers and Chris Farley were still castmembers.
She currently stars alongside SNL veteran Maya Rudolph in Up All Night, which airs Thursdays on the Peacock Network.
Applegate appears on this weekend's Saturday Night Live along with first-time musical guests Passion Pit.
Saturday Night Live airs at 11.30pm ET on NBC.