The 25-year-old left the show in September 2007 when her character drove off a cliff in dramatic stunt which subsequently won 'Spectacular Scene Of The Year' at last year's British Soap Awards.
At the same ceremony, Bissix also walked away with the award for 'Best Exit'.
Clare's return to Hollyoaks village is to tie in with the departures of old flame Warren Fox (Jamie Lomas) and the man who pushed her off The Loft balcony, Justin Burton (Chris Fountain).
As part of their exit, Clare is hell-bent on revenge and Warren and Justin quickly become embroiled in a blazing fire at The Loft.
Bissix returns to filming at Hollyoaks' Liverpool home Lime Pictures next week and will reappear on screens at the end of May.
Only days after bowing out of the Channel 4 soap on screen in September 2007, it was announced that she was to reprise her role as Clare Bates in EastEnders. Her stay was short-lived, however, and she announced her decision to move on in May the following year.
More recently, she appeared in ITV skating show Dancing on Ice, where she was the first female contestant to be voted off.
> Click here to read our recent interview with Gemma Bissix