In order to investigate the effect of Cd²⁺ and Cu²⁺ stress on digestive enzyme activity of Tegillarca granosa.enzyme analytical method was conducted to analyze the changes of the digestive enzyme activity of Tegillarca granosa exposed to different concentrations of Cd²⁺ or/and Cu²⁺ for 30 days. The concentrations of heavy metal ion Cd²⁺, Cu²⁺, and their combination (Cd²⁺+Cu²⁺) were set as one, two, five, and ten times of the corresponding maximum limit values according to the Water Quality Standard for Fisheries (GB 11607). The results showed that compared with the blank control groups, when Tegillarca granosa were exposed to low concentrations of Cd²⁺, Cu²⁺ and (Cd²⁺+Cu²⁺), their digestive enzyme activity increased at the early experimental period (or be induced), and then decreased at the later period (or be inhibited); when the Tegillarca granosa samples were exposed to high concentrations, the amylase activity decreased from the start and kept low level all along. For the same heavy metal ion, the toxicity of the high concentration groups was higher than that of the low concentration groups in the amylase activity analysis. In the comparison of the two heavy metal ions and their combination, the toxicity of the Cu²⁺ group was highest, followed by the (Cd²⁺+Cu²⁺) group, and the Cd²⁺ group was lowest. The lipase activity of Tegillarca granosa increased at the early experimental period, and then decreased moderately or weakly at the later period. For the same heavy metal ion, the toxicity of the high concentration groups was higher than that of the low concentration groups in the lipase activity analysis. In the comparison of the two heavy metal ions and their combination, the toxicity of the (Cd²⁺+Cu²⁺) group was highest, followed by the Cu²⁺ group, and the Cd²⁺ group was lowest. The pepsin activity of Tegillarca granosa increased at the early experimental period. In the middle period, the activity had the variance of being increased, decreased, increased again, and then decreased. At the later period, the activity increased weakly, decreased moderately, and decreased weakly for different ion groups. For the same heavy metal, the toxicity of the high concentration groups was higher than that of the low concentration groups in the pepsin activity analysis. In the comparison of the two heavy metals and their combination, the toxicity of the (Cd²⁺+Cu²⁺) group was highest, followed by the Cu²⁺ group, and the Cd²⁺ group was lowest. The results show that there were obvious stress of Cd²⁺ and Cu²⁺ in the environment for the digestive enzyme activity of Tegillarca granosa.