Johnson was substituted just 32 minutes into QPR's west London derby draw against Chelsea at Loftus Road on Saturday after a seemingly innocuous incident.
Following a scan, an injury to his anterior cruciate ligaments has been diagnosed, meaning he can expect to be on the sidelines for six months or perhaps even longer.
"Andy Johnson suffered an anterior cruciate ligament injury against Chelsea and is likely to be sidelined for the majority of the season," the club said via their official website.
"AJ felt something in his knee. We hope he's going to be okay, but it's a little bit of a worry," Hughes said after the game. "You need players like AJ in the squad because they give so much."
The 31-year-old joined QPR from neighbours Fulham in the summer on a free transfer, and has appeared in three of the club's first four Premier League games of the season so far.
Johnson has a history of severe knee problems. He missed most of the 2009/10 campaign with a similar injury.