〔Abstract〕 Objective To investigate the molecular mechanisms by which kaempferol induces apoptosis in hepatic stellate cells (HSC). Methods HSC were divided into five groups: blank control, transforming growth factor-β1(TGF-β1) (10 ng/mL) group, and groups treated with different concentrations of kaempferol (8, 16, 32 µmol/L). Cell counting kit-8(CCK-8) assay was used to evaluate chrysin's effect on HSC proliferation. Transwell assay was used to assess chrysin's impact on HSC migration. Flow cytometry was used to detect apoptosis, reactive oxygen species (ROS) expression, and mitochondrial permeability transition pore (mPTP) opening across groups. 5,5,,6,6,-Tetrachloro-1,1,,3,3,-tetraethylimidacarbocyanine iodide(JC-1) assay was used to test mitochondrial membrane potential. Western blot was used to detect apoptosis-related mitochondrial proteins and extracellular matrix protein expression. Transmission electron microscopy was used to examine mitochondrial structural alterations. Molecular docking and kinetic simulations was used to analyze the targeted interaction between kaempferol and NAD-dependent deacetylase sirtuin-3 (SIRT3). Results Kaempferol significantly inhibited the proliferation and migration of HSC while promoting their apoptosis. It markedly increased ROS expression and opened the mPTP in these cells, concurrently reducing their mitochondrial membrane potential. It increased the expression of Bcl-2 associated X protein (Bax), Cleaved-Caspase3, and Cleaved-Caspase9 while decreasing the expression of B lymphocytoma-2 (Bcl2) and SIRT3. Kaempferol promoted mitochondrial fission in HSC. Molecular docking and kinetic simulations revealed that kaempferol exhibits favorable binding affinity and stability with SIRT3. Conclusion Kaempferol induces HSC apoptosis by targeting SIRT3 to mediate ROS regulation of the mitochondrial apoptosis pathway, thereby reducing extracellular matrix deposition. This demonstrates kaempferol's potential anti-fibrotic effects in liver.