Abstract: As a clinical syndrome with systemic manifestations, acute kidney injury (AKI) is characterized by a sharp decline in glomerular filtration rate, high morbidity and mortality. However, the pathogenesis of AKI has remained elusive. Mitochondrial dysfunction plays an important role in its progression. And silence information regulator 3 (SIRT3), a major deacetylase regulator of mitochondrial target proteins, ameliorates AKI through regulating mitochondrial biosynthesis, improving mitochondrial dynamics, inducing mitochondrial autophagy and reducing oxidative stress to maintain mitochondrial homeostasis. Elucidating the underlying mechanism of SIRT3-mediated mitochondrial homeostasis in AKI is of great significance for managing AKI and improving patient outcomes.