In this study, we provide new insights into the role of MUTYH in the pathogenesis of AKI using MUTYH knockout mice, overexpression of different types of human MUTYH in vivo, and cultured tubular cells with MUTYH knockout or overexpression in vitro, suggesting that MUTYH plays a protective role in cisplatin‐ or FA‐induced AKI by preventing cellular DNA damage and mitochondrial dysfunction. The gene discussed is MUTYH; the disease is acute kidney injury.