The musician will be performing on the late night show's upcoming fifth series, which airs in the autumn.
On Tuesday, July 31, Lethal will perform a special VIP gig in Liverpool which is to be filmed for the programme.
Hollyoaks fans are also being invited to watch his performance and feature in the series themselves.
Show chiefs have confirmed that the filming will feature Hollyoaks sixth formers Jono (Dylan Llewellyn), Neil (Tosin Cole) and Bart (Jonny Clarke).
Lethal Bizzle's appearance comes after hip-hop star Wretch 32 and singer-songwriter Maverick Sabre both recently featured in the main 6.30pm show.
Hollyoaks Later was officially recommissioned for another series in May. As well as the sixth form boys, this year's series will feature Brendan Brady (Emmett Scanlan), Walker (Neil Newbon) and Mitzeee (Rachel Shenton).
Full details of how to apply for tickets to the Lethal Bizzle gig can be found on the Hollyoaks website.