Cadmium accumulation in rice grain poses a serious threat to people’s health. Understanding the genetic basis on grain cadmium accumulation facilitates efforts to reduce it. Here, we show that OsCd1 is involved in Cd uptake and contributes to grain accumulation in rice. Natural variation in OsCd1 with a missense mutation Val449Asp is responsible for the divergence of rice grain cadmium accumulation between japonica and indica. Notably, near-isogenic line tests confirmed that the indica variety carrying the OsCd1^V449 allele could reduce the grain cadmium accumulation. The favorable allele OsCd1^V449 may be an important genetic resource to reduce grain cadmium accumulation for indica.