Cadmium (Cd) is one of the most toxic heavy metals that are widespread in inshore sediments of China, and can induce the production of toxic hydroxyl radicals that cause cell damage. The present study investigated the effect of two Cd concentrations (the final Cd concentration of 0.025 and 0.05 mg/L, prepared with CdCl2 x 2.5H2O) on metallothioneins (MT), antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and DNA integrity (DNA strand breaks) for up to 15 days in the gills and hepatopancreas of the portunid crab Charybdis japonica. The result indicated that MT was significantly induced after 3 days, with a dose-response relation between MT contents and Cd concentrations in two tissues and has a time-response relation in hepatopancreas during the experimental period; SOD, CAT and GPx activities could be stimulated after 0.5 day, all attained peak value and then reduced during the experimental period, but were not inhibited at day 15, except SOD and CAT in gills. Gill was more sensitive to Cd than hepatopancreas, and the hepatopancreas was the main detoxification tissue to deal with oxyradicals. DNA strand breaks were induced after 0.5 day, and there was a positive dose-response relation between DNA damage levels and Cd concentrations in gills, rather than hepatopancreas due to higher DNA repair activities. These results suggest the mechanisms of Cd toxicity and detoxification strategies in both tissues of C. japonica; in addition, the use of the biomarkers as indices for biomonitoring potential toxic effect of Cd in situ is discussed.