LAPD says the shooting happened near Beswick and Calzona streets just before 10:30 p.m.
The incident prompted a brief closure of southbound lanes of the 5, but lanes reopened at about 11:20 p.m.
Details of what led up to the shooting and a suspect description were unavailable.
The victim is believed to be in his 30s, police said.
Homicide detectives were at the scene investigating.