Harry Redknapp is the huge favourite with bookmakers to take over.
The West London club said in a statement on their website that Hughes had left the club with immediate effect after drawing four and losing eight times so far.
"This decision has been taken after careful consideration by the Board of Directors, following numerous meetings over the last few days," the statement said.
"Mark has shown integrity and professionalism throughout his time here, but ultimately the circumstances we find ourselves in have left the Board of Directors with very little choice but to make a change."
Speculation has mounted in recent weeks that Hughes would be shown the exit door after a woeful start to the season that sees QPR as the only club without a win in all four professional divisions in England.
They narrowly avoided relegation from the Premier League on the final day of last season.
Club owner Tony Fernandez had publicly backed Hughes, although there was a change in tone after Saturday's home defeat to fellow strugglers Southampton which left them four points adrift at the bottom of the table.
"I feel gutted," Fernandes wrote on Twitter.
"I have put my heart and soul into this with my other shareholders. And done all we can to give support to players and all management. I can only apologise to the QPR fans. We keep fighting.
"Let me tell you fans come first. Everyone including me let the fans down. Many of us need a hard look at themselves."
Many fans had become increasingly opposed to Welshman Hughes remaining in charge, with banners in favour of former Tottenham Hotspur manager Redknapp displayed by supporters at the club's Loftus Road ground on Saturday.
Hughes joined the club in January and after ensuring the club's top-flight status, embarked on a squad overhaul in the close season which saw South Korean captain Park Ji-sung sign from Manchester United, midfielder Esteban Granero join from Real Madrid and winger Junior Hoilett move from Blackburn, among others.
However, many of the new arrivals have failed to settle, while injuries have also affected the team.
Mark Bowen and Eddie Niedzwiecki will take charge of the trip to Manchester United in the Premier League on Saturday, the club said.
"The Board will now be working actively to put a new managerial structure in place as soon as possible."
