The two rappers have been competing for record sales for a number of years, but the rivalry looks set to step up a notch after 50 Cent's latest comments.
The Daily Mail reports that the 37-year-old made the off-colour remark when asked by XXL magazine for his thoughts about Kardashian and West's new song 'Perfect Bitch'.
He said: "You know how it is? One man's trash is another man's treasure."
The Get Rich or Die Tryin' star then continued: "I mean, if that man feel like she's perfect, then she's perfect. He could mean it and you'll end up singing the words to it because he's Kanye."
He then left on an ominous note of caution, claiming that "the smartest guys I know have lost being a bad judge of character in that area".
The feud between the pair has been on and off for a number of years, with 50 Cent threatening to quit the music business if West's album Graduation outsold his album Curtis.
West has previously compared being insulted by 50 Cent to like "being spat on by a little kid".
Watch Kanye West's video for 'Can't Tell Me Nothing' below: