Objective：This study aims to study the inhibitory effect of α7 nicotinic acetylcholine receptor（α7-nAChR）on chondrocyte apoptosis，providing a new idea and research strategy for the clinical treatment and study of osteoarthritis（OA）. Methods：Mice were randomly divided into the following groups：control group，monosodium iodoacetate（MIA） treatment alone group，MIA+Nic（Nicotine 0.5 mg/kg or 1 mg/kg）treatment group and MIA+Nic+MLA（methyllycaconitine）treatment group. A mouse model of OA induced by injection of MIA was used to study the effects of nicotine on joint pain，cartilage degeneration and chondrocyte apoptosis. Mechanical withdrawal sensitivity was detected using Von Frey hairs at 7，14，and 21 days after MIA injection. Cartilage degeneration was assessed using cartilage degeneration score and aggrecan loss score at 21 days after injection. Apoptosis of articular cartilage was determined by terminal deoxynucleotidyl transferase dUTP Nick end labelling（TUNEL） staining. Meanwhile，Western blot was used to detect the expression of apoptosis-related proteins Bcl-2，Bax，cleaved caspas-9 and caspase-9. Results：After model preparation of 21 days，the latency threshold of mechanical foot retraction reflex in MIA group decreased significantly to（0.28 ± 0.02）g，the scores of articular cartilage degeneration and proteoglycan loss increased to （5.33 ± 1.19） and （2.33 ± 0.27），respectively，and the apoptosis rate of articular chondrocytes increased to（31.83 ± 3.89）%. Nic（1.0 mg/kg）treatment reduced pain behavior（P < 0.05），cartilage degeneration（P < 0.05） and chondrocyte apoptosis induced by MIA（P < 0.05）. In addition，nicotine treatment reduced MIA-induced down-regulation of Bcl-2，up-regulation of Bax and cleaved caspase-9/caspase-9 ratio levels（P < 0.05）. The benefit of nicotine was abolished by a selective α7 nicotinic receptor blocker MLA in vivo. Conclusion：The activation of α7-nAChR has a protective effect on cartilage damage in OA model mice and exerts an anti-chondrocyte apoptosis effect by inhibiting the mitochondrial apoptotic pathway.