People heard an explosion from the area of the Federated Co-op refinery around 3:30 p.m. local time.
Deputy fire Chief Gerard Kay tweeted that "all personnel accounted for and no injuries reported."
He says the focus is on putting out the fire.
The blast could be heard and felt all over Regina and outside the city as well.
One woman from Pilot Butte, about 20 kilometres east of Regina, called radio station CKRM.
"From out here, we heard it and was like, 'what the heck's that? And then my son called me shortly after because he was on his way in to the city and they were right by the refinery and he said his whole truck just shook and they felt the vibrations in their chest," the woman said.
Larry Shrader lives in Regina.
"I'm a mile away from it and my house shook, the front window shook, my Christmas tree shook; scared the heck out of all of us," he said.
It's the fourth fire in about two years at the refinery.
In February, a fire in a coker unit sent flames shooting nearly 20 metres in the air, but was quickly brought under control.
In October 2011, corrosion in a pipe triggered a fireball that sent seven contract workers to hospital and forced 1,400 workers from the facility. No one was injured.
In May 2012, a much smaller fire occurred when an overheated crude oil pump ignited. There were no injuries.
Also on HuffPost