Abstract: Objective: Osteoarthritis (OA) is a prevalent chronic joint disease. The purpose of this study was to investigate the proliferative and anti-inflammatory effects of Tremella fuciformis polysaccharide on osteoarthritis cell model human chondrocyte T/C-28a2. Methods: Proliferative effect and cytotoxicity of T/C-28a2 cells treated by Tremella fuciformis polysaccharide were detected with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) and crystal violet staining experiment. The bone inflammation model was established by lipopolysaccharide (LPS) treatment in T/C-28a2 cells. The expression of interleukin-6 (IL-6) in cells after drug treatment was detected by enzyme-linked immunosorbent assay (ELISA) analysis. The expression of osteoprotegerin (OPG) and inflammatory factors after drug treatment was detected by Western blot analysis. In addition, reactive oxygen species (ROS) release assay was used to detect the level of oxidative stress and anti-inflammation response to cells. Results: Tremella fuciformis polysaccharide could promote proliferation of human chondrocyte T/C-28a2 without obvious cytotoxicity. After LPS was used to treat human chondrocytes to simulate the environment of bone inflammation, it was found that the treatment of Tremella fuciformis polysaccharide and chondroitin sulfate could reduce the secretion of IL-6 and inhibit the occurrence of inflammation. Further Western blot analysis showed that after treatment of Tremella fuciformis polysaccharide, expression of related osteoprotegerin (OPG) was upregulated, expression of proapoptosis-related protein Bax, extracellular signal-regulated kinase ERK-MAPK and nuclear factor κB (NF-κB) was down-regulated. ROS release experiment showed that Tremella fuciformis polysaccharide and chondroitin sulfate could inhibit intracellular ROS levels and the occurrence of inflammatory response. Conclusion: Tremella fuciformis polysaccharide exhibited the effect of inhibiting osteoarthritis, protecting cartilage tissue and resisting cell apoptosis to a certain extent. In this study, the anti-inflammatory effect of Tremella fuciformis polysaccharide and its mechanism were primarily explored, which provided the preliminary experimental basis for the development of Tremella fuciformis polysaccharide as an anti-inflammatory drug.