The move allows contractor Brookfield to work up designs and start early in the New Year on main construction of Scotland’s largest hospital.
Construction of an adjacent new laboratory facility started earlier this year.
Public health minister Shona Robison said: “The new South Glasgow Hospitals is Scotland’s biggest-ever hospital building project and will be entirely publicly funded.
“It’s great news for people throughout the West of Scotland that this important project has been given the final go-ahead.
“In the current economic climate, this significant investment is a clear signal that the Scottish Government is continuing to prioritise spending on our NHS to improve patient care.”
The 14-storey hospital will cover 28ha and centralise acute services currently provided by three hospitals.
When finished in 2015, it will boast more than 1,300 beds and will include a 256-bed children’s hospital.