Cadmium (Cd) is a well-known toxic heavy metal that accumulates in the aquatic environment. Cd has been reported to induce oxidative damage and apoptosis. We investigated the regulation mechanism of hydrogen peroxide (H 2 O 2 ) on Cd-induced apoptosis. We show that in the gills of the freshwater crab Sinopotamon henanense Cd induced apoptosis, in a time- and concentration-dependent manner, as confirmed by DNA fragmentation analysis and transmission electron microscopy. Additionally, Cd caused production of H 2 O 2 after 2h of treatment at 58mg L −1 Cd, and significantly increased the caspase-3/8/9 activity in crabs relative to the control group. Pre-treatment with the scavenger for H 2 O 2 , dimethylthiourea (DMTU) and antioxidant, N-acetyl cysteine (NAC), effectively inhibited the activities of caspase-3 and caspase-9, eventually blocked Cd-induced DNA fragmentation and the appearance of markers for apoptotic cell death. These results suggest that Cd might induce intracellular H 2 O 2 generation to trigger the crab apoptotic processes by regulating the activities of caspase enzymes.