Previously we reported that (Z)-3-(chloromethylene)-6-methylthiochroman-4-one (CMMT), a novel thiochromanones derivative could exhibit dramatically antitumor activities on 12 human tumor cell lines in vitro. How was CMMT kill the tumor cells? The purpose of this study was to answer this question. Pretreatment of Hela cell cultures with 5, 10, 20μmol/L CMMT for 24h, afforded significant apoptosis induction as judged by Flow cytometry assay, and Hoechst 33258 fluorescence staining. We found that CMMT could cause cancer cell death, in particular apoptotic cell death. Mechanistically, CMMT increased production of cysteinyl aspartate specific proteinase including Caspase-3, Caspase-8 and Caspase-9, and death receptors (DR3) underlay apoptosis induction effect. Taken together, these results suggest that CMMT kills tumor cells by apoptosis induction via increasing production of caspase-3 Caspase-8, Caspase-9, and death receptors 3.