Acute kidney injury (AKI) is a common and serious kidney disease with rising incidence and mortality rates. Disruption of fatty acid oxidation (FAO) is a significant pathological feature in the progression of AKI. Under AKI conditions, renal tubular epithelial cells (RTECs) undergo marked energy metabolic reprogramming, with particularly notable disturbances in fatty acid metabolism. Therefore, exploring the mechanisms associated with impaired fatty acid metabolism is crucial for developing effective therapies for AKI. This review comprehensively discusses the alterations in lipid metabolism in AKI, including fatty substances and metabolic enzymes related to FAO. It summarizes the adverse reactions caused by FAO metabolic reprogramming, such as autophagy, apoptosis, inflammation, and oxidative stress in cells. The review proposes that supplementing FAO-related metabolic products or inhibiting FAO-related regulatory enzymes can effectively reverse abnormal metabolic processes in the kidneys, thereby reducing inflammation and oxidative stress, leading to effective treatment of AKI. This work provides insights that may facilitate further clinical research on AKI.