ObjectiveTo investigate the mechanism of quercetin in regulating chondrocyte extracellular matrix metabolism and inflammatory response in knee osteoarthritis （KOA） from the perspective of autophagy. MethodChondrocytes were extracted and cultured， and the primary cells were identified by immunofluorescence staining with collagen Ⅱ. The chondrocytes induced by lipopolysaccharide （LPS） were divided into a control group （without any treatment）， a model group （10 mg·L-1 LPS treatment for 48 h）， and low-， medium-， and high-dose quercetin group （10 mg·L-1 LPS treatment for 48 h combined with 50， 100， and 150 mmol·L-1 quercetin for 24 h）. The inhibitory effects of LPS （2.5， 5， 7.5， 10， 12.5 mg·L-1） on the proliferation of chondrocytes for different periods （24， 48， 72 h） were detected by cell counting kit-8 （CCK-8）. The effects of quercetin （50， 100， 150， 200 mmol·L-1） on the LPS-induced proliferation of chondrocytes for different periods （12， 24， and 48 h） were investigated. The expression of microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） and ubiquitin-binding protein p62 was detected by Western blot. LPS-induced chondrocytes were treated with 3-methyladenine （3-MA）. The resultant cells were divided into a control group （without any treatment）， a model group （10 mg·L-1 LPS）， a quercetin group （model group + 100 mmol·L-1 quercetin）， a 3-MA group （model group + 100 μmol·L-1 3-MA）， and a 3-MA + quercetin group （model group + 100 μmol·L-1 3-MA + 100 mmol·L-1 quercetin， specifically， LPS for 48 h， 3-MA for 2 h， and then quercetin for 24 h）. The content of interleukin （IL）-1β and tumor necrosis factor （TNF）-α was determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of matrix metalloproteinase 13 （MMP-13） and tissue inhibitor of metalloproteinase 1 （TIMP1） was detected by Western blot. ResultCollagen Ⅱ immunofluorescence staining showed that the extracted cells were consistent with the characteristics of chondrocytes. As revealed by CCK-8， the optimum concentration of LPS was 10 mg·L-1 with an action time of 48 h， and the optimum concentration of quercetin was 100 mmol·L-1 with an action time of 24 h. Western blot results showed that compared with the control group， the model group showed decreased expression of LC3Ⅱ （P<0.01） and increased expression of p62 （P<0.01）. The expression of LC3Ⅱ in the quercetin groups was higher than that in the control group （P<0.01）， especially in the medium-dose quercetin group. The p62 expression in the quercetin groups was lower than that in the control group （P<0.01）， especially in the medium-dose quercetin group. Compared with the control group， the model group showed increased expression of MMP-13 （P<0.05） and decreased expression of TIMP1 （P<0.01）. Compared with the model group， the quercetin groups and the 3-MA + quercetin group showed decreased expression of MMP-13 （P<0.05， P<0.01）， especially the quercetin groups， and increased expression of TIMP1 （P<0.01）， especially the quercetin groups. Morphological changes in chondrocytes under the inverted microscope showed that quercetin could restore the morphology of damaged chondrocytes. CCK-8 showed that compared with the control group， the model group showed inhibited chondrocyte proliferation （P<0.01）， and compared with the model group， the quercetin groups and the 3-MA + quercetin group showed promoted chondrocyte proliferation （P<0.01）， especially the quercetin groups. ELISA results showed that IL-1β and TNF-α levels in the model group were higher than those in the control group （P<0.01）， and the levels of IL-1β and TNF-α in the quercetin groups and the 3-MA + quercetin group were lower than those in the model group （P<0.05， P<0.01）， and the decrease in the quercetin groups was the most significant. ConclusionQuercetin can promote LPS-induced chondrocyte proliferation， regulate chondrocyte extracellular matrix synthesis and metabolic balance， inhibit the inflammatory response， and restore chondrocyte function. The mechanism may be related to the activation of autophagy by quercetin.