Heme oxygenase-1 (HO-1) is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe²⁺), carbon monoxide (CO), and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI). The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI), and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.