2010 Regional League Division 2 Southern Region is the 2nd season of the League competition since its establishment in 2009. It is in the third tier of the Thai football league system. The league has been expanded from 8 clubs in 2009 to 14 clubs this season. The league winners and runners up will qualify for the 2010 Regional League Division 2 championship stage.
Narathiwat were promoted to the 2010 Thai Division 1 League after coming 3rd in the 2009 Regional League Division 2 championship pool.
Surat Thani were relegated from the 2009 Thai Division 1 League after finishing the season in 14th place.
Prachuap Khiri Khan re-located from the Regional League Central-East Division 2009 into the Southern Division.
Trang, Ranong, Phang Nga, Chumphon and Hat Yai joined the newly expanded league setup.
Prachuap Khiri Khan pulled out citing insufficient budget and concerns about safety before the season commenced. They had just been relocated from the Regional League Central-East Division.
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