The shooting occurred about 3:30 a.m. at a nightclub in the 2200 block of Cahuenga Boulevard, according to the Los Angeles Police Department.
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About 30 people were inside at the time, most of who escaped through the front and rear exits of the building.
Investigators said two men wearing ski masks entered the establishment during an illegal poker game. The security guard brandished a gun and was fatally shot by one of the suspects, said an LAPD spokesperson.
"One of the suspects basically shoots him right as he walks in the door," LAPD Detective Richard Moakley told reporters at the scene. "This may have been like a botched robbery attempt."
The suspects were inside the building for less than two minutes, Moakley said. They fled down a back alley without taking any property.
"There's multiple things here, it's two stories," said Moakley. "May have been a hookah lounge on the top story and some sort of gambling operation on the bottom."
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The victim was pronounced dead at the scene. He was not immediately identified.
Detailed descriptions of the two suspects were not immediately available.
According to LAPD data analyzed through our ABC7 Neighborhood Safety Tracker, in the last 12 months, there have been 11 homicides reported by the LAPD North Hollywood Division, which covers this area.
Anyone with information is urged to contact police.