AIM: To investigate the effect of Caragana sinica root (CSR) on ferroptosis in the Erastin-induced chondrocyte ferroptosis model and possible mechanisms. METHODS: The C28/I2 chondrocyte cell line was cultured to construct a cell model of Erastin-induced ferroptosis. Cell viability was detected by MTT assay; cell death was observed by Calcein/PI staining; cell lactate dehydrogenase (LDH) and total glutathione (GSH) levels were detected by the kit; reactive oxygen species (ROS) levels were detected by fluorescent probe BODIPY 581/591 C11 labeling; mitochondrial membrane potential (ΔΨm) changes were observed by Rh123 and JC-1 staining; Western blot was used to detect the expression of ferroptosis-related proteins (ACSL4, GPX4) and TRPM7 proteins. RESULTS: Erastin treatment decreased chondrocyte viability, increased cytotoxicity, induced oxidative stress, disrupted ΔΨm, and up-regulated ACSL4 protein expression, while down-regulating GPX4 protein expression and inducing chondrocyte ferroptosis. In contrast, CSR restored cell viability and reduced oxidative stress, thereby inhibiting chondrocyte ferroptosis. In addition, CSR reduced the Erastin-induced increase in TRPM7 protein expression level. CONCLUSION: Erastin induced lipid peroxidation in C28/I2 chondrocytes, causing mitochondrial damage and ferroptosis; CSR may inhibit chondrocyte ferroptosis by blocking TRPM7, thus exerting a protective effect on chondrocytes.