BACKGROUND: Cadmium (Cd) is a toxic heavy metal for all organisms. Increasing of wheat grain accumulates Cd posing a serious risk to human health. Thus, reducing grain Cd concentration of wheat is urgently required for food security and human health. Here, we found a wheat yellow stripe-like protein 15 (YSL15-6B) governs grain Cd concentration. METHODS: The expression pattern, subcellular localization, Cd transport activity and Cd accumulation in mutant and overexpressing lines of wheat YSL15-6B were analyzed. RESULTS: TpYSL15-6B, cloned from Dwarf Polish wheat (Triticum polonicum L. 2n = 4x = 28, AABB), was mainly expressed in roots and leaves. Its protein was localized at the endoplasmic reticulum and plasma membrane in protoplast. Expression of TpYSL15 in yeast increased Cd concentration under Cd-NA stress. Loss-of-function of TtYSL15-6B in 'Kronos' increased Cd uptake, root-to-shoot Cd translocation, and grain Cd concentration. Meanwhile, Ttysl15-6B mutant line exhibited up-regulation of TtNRAMP5 and TtHMA2, and down-regulation of TtZIP1 when compared with the wide type. Overexpression of TpYSL15-6B in rice caused Cd exporting from roots, and limited root-to-shoot Cd translocation and grain Cd concentration. TpYSL15-6B-overexpressing lines showed up-regulation of OsZIP1 and OsABCG36, and down-regulation of OsIRT1 and OsNRAMP2 when compared with the wide type ZH11. CONCLUSION: wheat YSL15-6B governs Cd export from plant. These results provide a new gene and insight for limiting grain Cd concentration in wheat and the physiological pathway of Cd transport.