Conflicting data regarding the ability of hydrogen sulfide (H 2 S), which reaches high levels in the large intestine owing to biosynthesis in the intestinal cells and intestinal bacteria, to promote or inhibit colorectal cancer cell proliferation have been reported recently. In the present study, the effect of H 2 S on the proliferation of the human colorectal cancer cell line Caco-2 was examined by using the H 2 S donor GYY4137. At concentrations of 0.5 mM and 1.0 mM, GYY4137 significantly inhibited Caco-2 cell viability. Cell cycle analysis, and apoptosis and necrosis detection revealed that the anti-proliferative effect of GYY4137 was partially attributable to the induction of S-G 2 /M cell cycle arrest, apoptosis and necrosis. These results suggest that H 2 S has the potential to suppress human colorectal cancer cell proliferation by influencing both cell cycle and cell death.