The band will play an intimate set at the iconic restaurant to celebrate its 40th anniversary in collaboration with Absolute Radio.
The one-off show is part of a series of events held at the legendary venue and will take place from 7pm on December 13.
Absolute DJ Pete Donaldson said: "You Me At Six have already made a name for themselves as a solid British rock band.
"Their first two records were fantastic, and Sinners Never Sleep is set to be another huge hit for the group.
"The gig at Hard Rock Cafe will be a great chance for fans to see the guys up close and completely in their element."
Tickets for the gig can be won by tuning in to Absolute Radio or by visiting the Back Room London Facebook page.
> You Me At Six: 'New album Sinners Never Sleep made us ill'
> You Me At Six perform Foo Fighters medley - listen
Watch the music video for You Me At Six's 'Loverboy' below: