OBJECTIVE: To investigate the role of lupeol in mitigating chondrocyte senescence in osteoarthritis (OA) by regulating autophagy through the sirtuin 3 (SIRT3)/mechanistic target of rapamycin kinase (mTOR) pathway. METHODS: Knee articular chondrocytes from primary-generation mice were isolated and divided into different groups, including a control group, a lupeol group (given 2.5, 5, 10, 20, and 40 μmol/L lupeol), a tert-butyl hydrogen peroxide (TBHP) group (receiving 50 μmol/L TBHP), TBHP + lupeol group, TBHP + lupeol + chloroquine (CQ) group (receiving 20 μmol/L CQ, an autophagy inhibitor), TBHP + lupeol + si-NC group, and TBHP + lupeol + si- RESULTS: Based on the results of cell viability assay, 20 μmol/L lupeol treatment for 24 h was identified as the optimal intervention concentration and duration. Compared with that in the TBHP group, cell viability was elevated in the TBHP + lupeol group ( CONCLUSION: Lupeol alleviates chondrocyte senescence in osteoarthritis by regulating autophagy through the SIRT3/mTOR pathway.