"We would like to express our thanks to Mark and his staff for all of their efforts during their time at St Mary's", a statement published on Southampton's Twitter account said.
"The search for a new manager to take the club forward is already underway", it added.
Hughes, who was sacked from Stoke City in January, took over at St Mary's in March with the team one point above the relegation zone.
During Hughes' spell in charge, the Saints won just once in 22 league games, although he did lead them to the last four of the FA Cup, where they lost to eventual winners Chelsea.
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