The 22-year-old made his professional debut for the Eagles against Barnsley in October 2008 before making the move to St Mary's Stadium last summer.
Ian Holloway's men pitch up on the South Coast this afternoon, and the England Under-21 international believes that they have what it takes to survive in the Premier League this season.
"I am excited to be playing against them for the first time since moving to Southampton, it should be a good match," Clyne told Sky Sports News. "Hopefully we get away with three points.
"I owe them a lot, the club I came through the ranks and they gave me the opportunity and I developed there as a player.
"I have watched them throughout last season and saw how well they were playing and they deserve everything. They have got a lot of new players and I think they can stay clear of relegation."
Clyne was named Palace's player of the year in 2011.