The rapper, 38, appears on ScHoolboy Q's track "That Part", and delivers a line about his reality TV star wife getting angry after he visits a strip club.
"Wifey gonna kill me, she the female O J," he raps in a clip.
The song was released on May 12 and neither West nor Kardashian have commented on the lyrics.
Kardashian's father Robert Kardashian was part of the defence team for the former NFL player when he was charged with the murder of ex-wife Nicole Brown Simpson and Ronald Goldman in 1994.
Kardashian and her family were very close to the disgraced sportsman, and even called him Uncle O J. It was also shown in the TV series that O J tried to commit suicide in the Kardashian home after being arrested for the murder of his ex-wife and her friend.
O J was jailed in 2008 for kidnap and armed robbery, and is eligible for parole in 2017.