Cadmium (Cd) accumulation in rice grain poses a serious threat to human health. While several transport systems have been reported, the complexity of rice Cd transport and accumulation indicates the necessity of identifying additional genes, especially those that are responsible for Cd accumulation divergence between indica and japonica rice subspecies. Here, we show that a gene, OsCd1, belonging to the major facilitator superfamily is involved in root 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 Cd accumulation between indica and japonica. Near-isogenic line tests confirm that the indica variety carrying the japonica allele OsCd1^V449 can reduce the grain Cd accumulation. Thus, the japonica allele OsCd1^V449 may be useful for reducing grain Cd accumulation of indica rice cultivars through breeding.