The blaze broke out just after noon Friday at a restaurant and club at the Southwest Inn on U.S. 59, one of Houston's most heavily traveled expressways. Flames spread to the motel and were shooting from the roof before firefighters extinguished the blaze about two hours later.
Field reports indicate that the firefighters were caught in a roof collapse, an official said. Three firefighters were killed at the scene, while the fourth died at a hospital, according to the mayor's office. One of the firefighters is a woman, the second female firefighter to die in the line of duty in the Houston Fire Department.
"Houston firefighters mourn the loss of our three brothers and our sister and will forever honor their sacrifices," said Jeff Caynon, president of the Houston Professional Firefighters Association in a statement. "This tragedy underscores the inherent dangers of our profession. Please keep Houston firefighters in your thoughts and prayers."
Fire Chief Terry Garrison said the four firefighters who died were looking for people they thought were still trapped in the burning building. Garrison said the firefighters "took the highest amount of risk possible" because they thought there were "civilians in the structure" when the roof collapsed.
Of the six hospitalized firefighters, one remains in critical condition, and the other five firefighters are in stable condition.
Temperatures in the low 90s and high humidity hampered firefighting efforts. Smoke from the fire snarled traffic.
The cause of the fire is unknown at this time.
KTRK and The Associated Press contributed to this report.