There were several explosions in Lac-Megantic, a town of about 6,000 people about 155 miles east of Montreal, QMI Agency reported. About 1,000 people were told to evacuate their homes and oil spilled into the Chaudiere River, the news agency said.
QMI said Quebec provincial police confirmed one person was dead. Lt. Michel Brunet said "several people" were missing, but wouldn't provide a specific number. The news agency said dozens of people told it family members were missing.
The Montreal, Maine and Atlantic Railway said the crew had left the train parked in Lac-Megantic about 11:30 p.m. Friday. No one was on board when it started moving.
The Canadian Broadcasting Corp. reported residents described buildings that had been gutted by explosions.
Lac-Megantic Mayor Colette Roy-Laroche tried to reassure local residents at a news conference Saturday, CNN reported.
"When you see the downtown of your city almost destroyed you think, how are we going to get through this?" she said. "But I can assure everyone here that all the authorities and ministries have been very supportive. We've deployed all the resources possible."
Canadian and American firefighters showed up to battle the blaze.
The fire created a large plume of smoke over the town, prompting environmental emergency services to send a mobile lab to check for airborne toxins, CNN said.
The cause of the derailment was not reported. The Office of Transportation Safety Board of Canada will investigate.
Authorities banned maritime traffic on the eastern shore of Lake Megantic because of oil in the lake and the Chaudiere River.
Why the train's brakes didn't keep the train from rolling on its own was unknown, a company spokesman said.
"That's what confuses us. How did this happen?" Joseph R. McGonigle, an executive at the Montreal, Maine & Atlantic, said. "There are many fail-safe modes. How this happened is just beyond us."
A Transportation Safety Board of Canada investigator told reporters he would be looking at the condition of the brakes, the tracks and the train's mechanical state.