New sulfonyl quinoxalines were designed and synthesized, followed by evaluating their anti-cancer activities in vitro. The synthesized sulfonyl quinoxalines were tested by utilizing kinase-glo luminescent assay, lance ultra assay and SRB assay. Nine target compounds were characterized by NMR and MS, but none of them showed inhibitory activity to PI3 Kα or mTOR. Among them, 3-(3-aminophenyl)sulfonyl-N-(3,5-dimethoxyphenyl)quinoxalin-2-amine(12), N-(3-(3-(3,5-dimethoxyphenyl) amino)quinoxalin-2-yl)sulfonyl-phenyl-acetamide(13), 1-(3-(3-(3,5-dimethoxyphenyl) amino)quinoxalin-2-yl)sulfonyl-phenyl-3-ethylurea(15) and N-(3-(3-(3,5-dimethoxyphenyl)amino)quinoxalin-2-yl)sulfonyl-phenyl morpholine-4-carboxamide(16) exhibited anti-proliferative activities against PC3 cell lines with IC₅₀<3 μmol/L. In conclusion, sulfonyl quinoxalines displayed moderate anti-proliferative activities for further investigation.