Goals from Rickie Lambert, Jason Puncheon and an own goal from Anton Ferdinand handed the Saints all three points at Loftus Road to leave the Rs still searching for a win
The hosts were unchanged from their narrow defeat against Stoke last time out, with Ryan Nelson managing to recover from a knee injury in time to feature at the back and Kieron Dyer making the bench following a calf strain.
The visitors were also unchanged as Nigel Adkins kept faith in the side that earned a point against Swansea, persisting with the 20-year-old Paolo Gazzaniga in goal despite his costly error last weekend.
Southampton started with the better of the action with two chances in the first 10 minutes, Lallana first blazing over after a lovely move and, just minutes later, an in-swinging cross from Puncheon finding its way on to the post.
Twenty minutes in and, following slack defensive play from QPR, another chance fell the hosts' way. From a corner, Lambert was left unmarked at the back post but the 30-year-old was unable to direct his header past Julio Cesar as the Brazilian tipped it wide.
From the ensuing corner, however, Southampton found the breakthrough. QPR were unable to clear their lines and the ball found its way to Cork in the area - a shot from the midfielder was skewed wide but Puncheon was there at the back post for what seemed like a routine tap-in. However, Jose Bosingwa thwarted the winger with a goalline clearance but, atoning for his earlier miss, Lambert was there to head home the rebound.
With the end of the first half in sight, Puncheon then added to QPR's dismay when, following excellent work from Nathaniel Clyne down the right and finding himself with time to spare on the edge of the area, the winger fired home a powerful effort to make it 2-0.
Predictably, QPR were booed off at half-time and Hughes acted positively, bringing on striker Jamie Mackie for defensive midfielder Alejandro Faurlin.
QPR started the second half strongly as Djibril Cisse forced a good save from Gazzaniga following a Taarabt cross and minutes later another excellent Taarabt cross put QPR back into the game.
The Moroccan picked up the ball on the left wing and delivered a superb in-swinger which proved too dangerous for Gazzaniga as he came and found himself nowhere near the ball, leaving Hoilett with a simple header.
The goal seemed to wake Southampton up as they reasserted themselves on the game once more with Puncheon causing problems and chances continuing to fall his way but he was unable to capitalise.
However, their dominance finally paid off in the 82nd minute as a short corner caught QPR unawares, resulting in a low ball being played across the penalty area that Ferdinand could only divert into his own goal to cap victory for the visitors and leave Hughes still searching for his first win of the campaign.