Breast　cancer　is　one　of　the　most　common　cancers　endangering　women＇s　health.　SRY-related　high-mobility-group　box　6　(SOX6)　is　associated　with　many　cancers,　though　its　role　has　not　been　reported　in　breast　cancer.　Here,　we　aimed　to　explore　the　expression　and　function　of　SOX6　in　breast　cancer.　On　the　basis　of　the　analysis　of　SOX6　in　The　Cancer　Genome　Atlas,　Cancer　Cell　Line　Encyclopedia　and　Genotype-Tissue　Expression　databases,　we　revealed　that　SOX6　was　downregulated　in　breast　cancer,　and　we　verified　the　results　at　the　cellular　level　by　means　of　western　blotting　and　quantitative　real-time　PCR.　When　SOX6　was　overexpressed,　the　proliferation　of　breast　cancer　cells　was　inhibited,　and　apoptosis　was　promoted.　Moreover,　the　methylation　level　of　the　SOX6　promoter　in　breast　cancer　was　significantly　higher　than　that　in　normal　tissues.　5　＇-Aza-2　＇-deoxycytidine　reversed　the　high　level　of　methylation　that　was　caused　by　decreased　expression　of　SOX6.　This　evidence　suggests　that　SOX6　is　a　tumor　suppressor　gene　associated　with　breast　cancer.　This　study　could　provide　a　new　target　for　breast　cancer　treatment.