After defeat to Stoke City yesterday, the Saints clash is a real six pointer for the Rs.
Hughes said: "Southampton is a huge game for us now. There is no doubt about that, but it was always going to be huge, now it is even bigger.
"It is a game that we have to win and we have to prepare ourselves all week to be ready to go. We have to prepare correctly like we do for all games.
"We have to make sure we are in the right shape and frame of mind heading into the Southampton game and make sure we get the three points.
"It's frustrating at the moment. I spoke to Tony Fernandes before the game, but I did not speak with him immediately after the game.
"We have had a lot of games lately where we have done really well and got nothing from them and we need to alter that."