Ten people, including five children aged three to 15, were killed in a fire in the early hours of Friday in a residential building in Vaulx-en-Velin, near the French city of Lyon, Interior Minister Gerald Darmanin said.
Another four people were seriously injured in the fire, which started on the ground floor before spreading up the seven-storey building, rescue authorities told local media.
The fire is now extinguished, but footage on social media showed a huge, dark cloud billowing above the building earlier in the day.
The blaze occurred around 3:00 am (0200 GMT), reports Reuters.
"I was awakened by the screams," a neighbour, Mohamed, told Le Progres de Lyon newspaper. "We wanted to help people but the smoke was too heavy. I saw a dead woman ... It's dramatic."
Darmanin said the cause of the fire was not known at this stage.
"There are several scenarios and a probe will be opened," said the minister, who is heading to the site.
A neighbour, Rida, told Le Progres de Lyon: "I told my kid not to go to school, he's shocked. It traumatised him to hear screams like that, screams of horror. My legs are shaking."
