The Phoenix Nights comedian, who presented previously in 2009, will return to front this year's ceremony at the Lowry Theatre in Salford Quays.
Laurie Mansfield, life president of the Entertainment Artistes' Benevolent Fund, teased: "The greatest artistes in entertainment have always featured on the Royal Variety Performance.
"And this year is no exception as the biggest acts in the world unite for one night only. There is something for everyone - a true Royal Variety Performance."
Singers Tony Bennett, Barry Manilow and Cee Lo Green will appear in the show, while comedian Jason Manford will also be in attendance.
Britain's Got Talent winner Jai McDowall will perform, as well as Pixie Lott and the magicians Penn & Teller.
The Royal Variety Performance, which takes place on December 5, will air on ITV1 later that month.