Live sea cucumbers (Stichopus japonicus) were irradiated under ultraviolet (UV) radiation (1.5 W/m2) for different times. Cathepsin L (CL), acetylcholinesterase (AChE), caspase-3, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), acid glutathione (GSH), protein carbonyl, and hydrogen peroxide (H2O2) contents in the intestinal tissue and body wall of the sea cucumber were analyzed. The results showed that after 6-h UV irradiation, the CL activities, H2O2 contents, and caspase-3 activities in the body wall and intestinal tissue increased by 69.27 and 52.37%, 2.44- and 3.57-fold, and 4.09- and 2.81-fold, respectively. The AChE decreased by 55.70 and 36.16%, respectively and the protein carbonyl contents in both body wall and intestinal tissue was 1.30-fold that of the control group. With increasing UV radiation time, SOD, CAT, and GPx activities in the body wall and intestinal tissue decreased by 38.79 and 24.70%, 44.27 and 36.18%, and 79.54 and 33.79%, respectively. The GSH contents increased by 75.31 and 66.71%, respectively. The results indicate that oxidative damage and apoptosis occurred with autolysis in S. japonicus under UV irradiation. ROS and related oxidation products played a fundamental role in the UV-induced autolysis pathway. This finding may improve the understanding of autolysis in S. japonicus.