The fire broke out just after noon at the Southwest Inn along the Southwest Freeway near Hillcroft.
According to a spokesperson for Houston Mayor Annise Parker, at least four firefighters have died, and five others are injured.
Firefighters can be seen searching the interior of the destroyed building. Firefighters at the scene are saluting, an honor given for a fallen comrade.
Witnesses tell Eyewitness News the fire began in a restaurant, although that has not been confirmed with officials. All patrons and employees of the restaurant reportedly got out safely.
The roof of the building has collapsed in areas. The structure houses a sports bar as well.
Thick black smoke coming from building could be seen for miles. The feeder is closed to inbound traffic. The main lanes of the SW Freeway are still getting by, but traffic is heavy in the area.
The Red Cross is on the scene providing assistance.
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