It has been documented that H 2 S, in some types of cancer, promotes tumor proliferation, whereas, in the other types, it inhibits the tumor cell growth. In the present study, we investigated the anti-cancer effects and relevant mechanisms of NaHS in C6 glioma cells. C6 cells were subjected to different concentrations of NaHS, then cell viability and morphological changes were examined by MTT assay and Hoechst staining. The protein expression of Caspase-3, Bcl-2, Bax, p38 MAPK (mitogen-activated protein kinase), and p53 was measured by Western blotting. This work demonstrated that NaHS could reduce cell number and induce apoptosis of C6 gliomas cells. The protein expression of Caspase-3 and Bax was up-regulated, while the protein expression of Bcl-2 was down-regulated. Additionally, p38 MAPK and p53 were activated in response to NaHS. Moreover, p38 MAPK inhibitor, SB203580, counteracted the inhibitory effect of NaHS on C6 glioma cells. These data suggest that NaHS can effectively reduce cell number of C6 cells by triggering the apoptosis via Caspase-dependent pathway. p38 MAPK and p53 play an important role in NaHS-induced apoptosis in C6 cells. These findings imply that administration of NaHS may represent a new strategy for the treatment of glioma.