Crews responded to 8686 Venice Blvd. at approximately 2 a.m. as both of the hotel's floors were burning, according to a Los Angeles Fire Department alert.
Once crews arrived to the scene, they encountered heavy fire in the first floor and smoke on the second. Firefighters saw residents attempting to escape, with some even breaking windows to get out.
"The outside of my door was in flames. As soon as I opened it, literally 'poof!' Flames got into my face," said Jemal Faruki, who jumped out of the window.
One person died, and two people - a man and a woman - were in grave condition, officials said. A fourth victim suffered injuries described as critical and two others suffered minor injuries.
About 105 firefighters responded to the blaze.
Firefighters knocked down the flames in approximately 39 minutes.
It was not immediately known how the fire started. Arson units are investigating and Los Angeles police will assist.
No firefighters were injured.