This study investigates the effect of baicalin (BAI) on ferroptosis in human osteoarthritis chondrocytes (OACs) induced by IL-1β and explores its underlying mechanism. BAI was found to inhibit IL-1β-induced ferroptosis in OACs by reducing intracellular Fe²⁺ accumulation, mitochondrial dysfunction, and the expression of ferroptosis-related proteins such as GPX4, SLC7A11, PS3, and ACSL4. Additionally, BAI reduced reactive oxygen species (ROS), lipid peroxidation (LPO), and malondialdehyde (MDA) levels, as well as collagen II degradation and MMP13 expression. The study also demonstrated that BAI activates the Nrf2 antioxidant signaling pathway, which is crucial for its protective effects against ferroptosis. When Nrf2 was knocked down using siRNA, the protective effects of BAI on IL-1β-induced ferroptosis were significantly weakened. These findings suggest that BAI can inhibit IL-1β-induced ferroptosis in OACs by activating the Nrf2 pathway, providing potential therapeutic targets for osteoarthritis.This study investigates the effect of baicalin (BAI) on ferroptosis in human osteoarthritis chondrocytes (OACs) induced by IL-1β and explores its underlying mechanism. BAI was found to inhibit IL-1β-induced ferroptosis in OACs by reducing intracellular Fe²⁺ accumulation, mitochondrial dysfunction, and the expression of ferroptosis-related proteins such as GPX4, SLC7A11, PS3, and ACSL4. Additionally, BAI reduced reactive oxygen species (ROS), lipid peroxidation (LPO), and malondialdehyde (MDA) levels, as well as collagen II degradation and MMP13 expression. The study also demonstrated that BAI activates the Nrf2 antioxidant signaling pathway, which is crucial for its protective effects against ferroptosis. When Nrf2 was knocked down using siRNA, the protective effects of BAI on IL-1β-induced ferroptosis were significantly weakened. These findings suggest that BAI can inhibit IL-1β-induced ferroptosis in OACs by activating the Nrf2 pathway, providing potential therapeutic targets for osteoarthritis.