Former cast members James Redmond (Rory 'Finn' Finnigan), Jeremy Edwards (Kurt Benson) and John Pickard (Dom Reilly) will all feature in the new run of after-dark specials.
This year's series has been tipped to take viewers "on an epic ride of Hangover-style proportions" as Tony Hutchinson (Nick Pickard) reunites with his old friends and his brother.
As he continues to battle cancer, Tony will team up with the gang alongside a host of unexpected and unhinged characters throughout Spanish and Moroccan locations.
Fans can also expect Esther Bloom (Jazmine Franks) and Tilly Evans (Lucy Dixon) to take centre stage in a "chilling" storyline as they celebrate an 18th birthday in a spooky location.
Elsewhere, Theresa (Jorgie Porter) will join up with a new recruit of the McQueen clan on a wild road trip.
Hollyoaks Later is currently in pre-production and is due to transmit in the autumn. As usual, five hour-long episodes will air on consecutive nights across one week in a post-watershed timeslot.
Jane Steventon, who took charge of last year's successful series, will once again be the show's producer. The series will be executive produced by Hollyoaks boss Bryan Kirkwood.
Kirkwood commented: "We are very happy to announce the commissioning of series six of Hollyoaks Later. It is a returning series that gives an annual late night treat to loyal Hollyoaks fans."
Lee Mason, Channel 4's editor for drama commissioning, added: "We're thrilled to be bringing back Hollyoaks Later for a sixth series and with it some of our best loved Hollyoaks faces.
"Tony's cancer battle is an important story for us to tell and we're so excited to be able to explore it further within the high octane, highly emotional and sometimes shocking world of Hollyoaks Later."
Digital Spy Soap Scoop video - press play below to watch Amie Parker-Williams reveal gossip on huge discoveries in Coronation Street and Emmerdale, a sinister newcomer in EastEnders, and more trouble from the Blakes in Hollyoaks.