Officers responded to a report of shots fired in the 1100 block of Naples Street at about 12:05 a.m., Officer Gordon Shyy said.
When officers arrived at the scene, they found two men suffering from gunshot wounds, Shyy said.
One of the victims, 43, was pronounced dead at the scene.
The other, 34, was transported to San Francisco General Hospital to be treated for multiple wounds to the upper body, Shyy said. His injuries are not considered life-threatening, he said.
Police are searching for one suspect, described as a white or Hispanic man last seen wearing dark clothing, Shyy said. The suspect fled the area on foot.
Anyone with information about the shooting is asked to call the San Francisco police at (415) 575-4444.
The homicide marks the city's third of the year.