Objective: To investigate the effects and mechanisms of kaempferol (KAE) on reducing lipid accumulation in hepatocytes under hypoxia. Methods: L02 cells were cultured in 1% O? for 24 h and then treated with KAE at different concentrations for 24 h. Oil red O staining and Nile red staining were used to detect lipid deposition. DHE fluorescent probe was used to measure the level of reactive oxygen species (ROS). JC-1 staining was employed to evaluate the changes in mitochondrial membrane potential. Western blotting was used to detect the expressions of superoxide dismutase and mitochondrial respiratory chain-related proteins. Results: KAE significantly reduced lipid accumulation (P<0.001), enhanced expressions of antioxidant enzymes, and improved mitochondrial electron transport chain (P<0.001) to maintain mitochondrial function in hepatocytes under hypoxia. Conclusion: KAE alleviates lipid accumulation in hepatocytes under hypoxia by maintaining mitochondrial function and alleviating oxidative stress.