Exogenous selenium (Se) can alleviate the toxicity of cadmium (Cd) in wheat plants. However, it remains elusive how the transformation of Se species influences the Cd accumulation in wheat grains. This study investigated the Cd accumulation and physiological mitigation in wheat plants at the reproductive stage under sodium selenite (Na2SeO3) fertilization through pot experiments. The results showed that soil Cd availability decreased with increasing bioavailability of Se in the presence of SeO32- . The decrease in wheat grain Cd content could be mainly attributed to the competitive absorption of soil Mn, formation of precipitates and complexes, and vacuolar sequestration of Cd in plants. Rapid shoot-to-grain Cd translocation mainly occurred at the milk stage, and the downregulation of TaNramp5 and TaHMA2 in roots respectively reduced Cd absorption and transport, while the upregulation of TaPCS1 and TaHMA3 promoted Cd immobilization in root vacuoles. When the Se content was controlled at 5 mg kg- 1 in Cd-contaminated soil (0.72 mg kg- 1), the Cd content decreased from 0.25 to 0.14 mg kg- 1 in wheat flour, while the Se content increased from 0.08 to 7.79 mg kg- 1. The findings provide important theoretical implications for safe and high-quality production of wheat in Cd-contaminated dryland soils.