Neighbors said they saw flames in the four-story house on Nguyen Thi Dinh Street in the city's Thu Duc City at around 1 a.m. and immediately started banging on the door and shouting to wake the occupants.
The fire spread quickly and engulfed the entire house within a few minutes, eyewitnesses said.
Luc Chan Tam, 54, the owner of the house who was sleeping outside, tried to save his family members, suffering burns in the process, but in vain.
"The victims were desperately screaming for help, but due to the heat of the fire, many people could not come close to the door to save them," said Hoai, a neighbor.
Fifty firefighters, four fire trucks and many ambulances were dispatched for rescue efforts. Firefighters broke open the door and found the bodies of Tam's wife, daughter-in-law, two children aged 25 and 27, and two grandchildren, one of them aged just one.
It is not known yet if they were burned to death or died of asphyxiation.
Police are investigating the cause of the fire.
Colonel Huynh Quang Tam, head of the HCMC Fire Prevention Police Department, said, "Five motorbikes parked at the entrance prevented the victims from escaping."
Ho Chi Minh City reported 290 fires last year in which 12 people died.