The scheme, which will be carried out by developer Umberslade, will see the construction of new homes, including affordable housing, shops and a public square during its first phase.
Plans for the overall scheme include up to 625 new apartments, a new hotel as well as 250,000 square feet of retail and office space.
The development has been stalled for the last five years because of a lack of available loan finance. HCA's investment is the largest to be made to date through the Get Britain Building programme, which has been set up to provide recoverable development funding to enable work on stalled sites with planning permission.
"This investment has played a significant part in helping unlock the continued development of what has been a huge success story for Bristol over the last 25 years," said Umberslade Managing Director Stuart Hatton in a statement. "We see this as a vote of confidence in what we are working to achieve and we're focused on ensuring that this investment makes a positive difference to the city centre."
"It is great news that work can continue at this vitally important project, which is delivering much needed high quality new homes and jobs for Bristol," said HCA executive director for the south and south west Colin Molton.
"The Harbourside has been a hugely successful project, which has transformed the former docks. This investment will build on that success by delivering new homes and safeguarding jobs that will be hugely welcome to the local economy," he said.
"This is crucial investment by the HCA that will kick-start further regeneration of Wapping Wharf and deliver important new and affordable housing on the Harbourside," said Bristol Mayor George Ferguson. "The potential for this site is enormous and I look forward to work starting soon and securing more Get Britain Building programme funding for the city."
Umberslade is expected to start work on the site in March this year and the first phase of the scheme is planned for completion in 2015.