There's no immediate word on what caused the explosion at the Imperial Sugar plant.
There are no reports of fatalities, but a spokesman for the Savannah-Chatham County police says there are "well over 50 to 100" injuries.
A hospital official says 30 to 35 patients are being treated for critical injuries.
A Coast Guard commander says shipping was shut down on the Savannah River while the waterway was searched for possible victims.
A machine operator who said she escaped from the third floor of the refinery, near the Savannah River, said there was fire "all over the building."
Imperial Sugar, based in Sugar Land, Texas, acquired Savannah Foods & Industries, which produced Dixie Crystals, in 1997.