In　this　work,　a　series　of　benzylsulfone　coumarin　derivatives　5a-5o　were　synthesized　and　characterized.　Kinase　inhibitory　activity　assay　indicated　that　most　of　the　compounds　showed　considerable　activity　against　PI3K.　Anti-tumor　activity　studies　of　the　active　compounds　were　also　carried　out　in　vitro　on　the　Hela,　HepG2,　H1299,　HCT-116,　and　MCF-7　tumor　cell　lines　by　MTS　assay.　The　structure-activity　relationships　(SARs)　of　these　compounds　were　analyzed　in　detail.　Compound　5h　exhibited　the　most　potent　activities　against　the　mentioned　cell　lines　with　IC50　values　ranging　from　18.12　to　32.60　mu　M,　followed　by　5m　with　IC50　values　of　29.30-42.14　mu　M.　Furthermore,　5h　and　5m　clearly　retarded　the　migration　of　Hela　cells　in　vitro.　Next,　an　in　silico　molecular　docking　study　was　conducted　to　evaluate　the　binding　models　of　5h　and　5m　towards　PI3K　alpha　and　PI3K　beta.　Collectively,　the　above　findings　suggested　that　compounds　5h　and　5m　might　be　promising　PI3K　inhibitors　deserving　further　investigation　for　cancer　treatment.