The US actress, who was 14 when she starred in the screen adaptation of Vladimir Nabokov's controversial novel, died on Thursday in Los Angeles.
Her death was confirmed to The New York Times by her friend Phil Syracopoulos, who gave no cause of death.
Lolita told the story of a young girl who was groomed by a middle-aged literature professor.
Lyon was reportedly selected to play the character Dolores Haze from a group of 800 auditionees, with Kubrick describing her as the "perfect nymphet."
The role, which she played opposite 53-year-old English actor James Mason, won her a 1963 Golden Globe for most promising female newcomer.
By the time the 18-rated film arrived in cinemas, the then 15-year-old Lyon was still too young to go and see it.
While she never achieved that level of success again, Lyon did also appear in John Huston's 1964 film The Night of the Iguana, where she played a teenager competing with several other women to seduce a disgraced preacher - played by Richard Burton.
She was married five times and is survived by her daughter Nona.
Her brief marriage to the convicted murderer Gary "Cotton" Adamson in 1973 made the headlines and she blamed the relationship on de-railing her acting career.
"I've been told by people in the movie business, specifically producers and film distributors, that I won't get a job because I'm married to Cotton," she reportedly said.
Her final movie role was playing an NBC newswoman in the 1980 horror film Alligator.