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Cadmium (Cd) contamination in soils poses great risks to both agricultural production and human health. Calcium (Ca) is an essential element playing a significant role in protecting plants against Cd toxicity. However, how Ca affects Cd uptake and translocation in rice is still not fully elucidated. In this study, the regulatory role of Ca in Cd uptake and upward translocation was investigated in rice at different growth stages. Our results showed that the supplement of 5 mM Ca significantly reduced Cd uptake by rice roots, because of their competition for Ca-permeable channels as an absorption site and Ca-induced downregulation of <i>OsNRAMP1</i> and <i>OsNRAMP5</i>. However, Ca application facilitated the upward translocation of Cd by both upregulating <i>OsHMA2</i> to induce xylem loading of Cd and downregulating <i>OsHMA3</i> to reduce vacuolar sequestration of Cd. Such contrary results suggested a double-edged role of Ca in regulating root Cd uptake and root-to-shoot Cd translocation in rice. Although it increased Cd content in the aboveground vegetative tissues during the whole growth period, the addition of 5 mM Ca eventually decreased Cd content in rice grains at the ripening stage. All these results suggest that Ca-based amendments possess great potential for the production of low-Cd rice grains.