Abstract: OBJECTIVE To investigate the antitumor effect of (Z)-3-chloromethylene-5-fluoro-thiochroman-4-ketone (CFTK) and (Z)-3-chloromethylene-5-methyl-thiochroman-4-ketone (CMTK) on the growth of human cancer cell lines (MCF-7, HepG-2, LS174T, A549, A375, 786-O, K562, U937) and mouse S180 cell line. METHODS Nine cancer cell lines were subjected to various concentrations of CFTK and CMTK, the inhibitory rates of CFTK and CMTK were measured by MTT assay. RESULTS CFTK and CMTK could dramatically exhibit antitumor activities at a low concentration (IC50 were (6.32±1.52) μmol·L^?1-(19.8±4.08) μmol·L^?1 and (7.16±0.76) μmol·L^?1-(18.2±5.28) μmol·L^?1). Importantly, the inhibition effects of CFTK and CMTK on nine cancer cells were much higher than cisplatin at the same concentration. CONCLUSION The results indicated that CFTK and CMTK can significantly inhibit cell proliferation and show extremely high antitumor activity in vitro, which provides preliminarily valuable data for further drug research and development.