As a kind of environmental pollutant, heavy metal Cadmium (Cd) exists widely in the environment. It is well known that Cd can accumulate and cause damage in liver, kidney and other organs. However, there are few studies on the immune cytotoxicity of Cd to fish. In particular, there are few studies on the toxicity of Cd to the head kidney lymphocytes of common carp. In order to further explore these mechanisms, we established an Cd exposure model in vitro. At the same time, we used the natural antioxidant astilbin (AST) to treat the cells to study its antagonistic effect on the toxicity of Cd. After exposure to Cd, the level of oxidative stress in head kidney lymphocytes increased, and the mRNA and protein expression of apoptosis-related markers Fas, FADD, Caspase8 and Caspase3 increased significantly (P < 0.05), which led to lymphocytes apoptosis. Hoechst staining and AO/EB staining also showed that the level of apoptosis increased after exposure to Cd. This is consistent with our previous research results. AST treatment reduced oxidative stress and apoptosis induced by Cd. In addition, oxidative stress inhibitor NAC could also reduce head kidney lymphocytes apoptosis induced by Cd, indicating that oxidative stress was involved in this process. Our results suggested that AST can alleviate the apoptosis of carp head kidney lymphocytes induced by Cd through oxidative stress. This study enriches the theoretical mechanism of Cd toxicity to fish head kidney lymphocytes, and puts forward a method to solve the toxicity of Cd, which provides a theoretical and research basis for the in vivo study of animal models in the future.