Baicalin (BAI) inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes (OACs) by activating the Nrf2 signaling pathway. Osteoarthritis (OA) is a degenerative disease involving articular cartilage, with chondrocytes (CHs) playing a key role in its progression. Ferroptosis, a type of iron-dependent cell death, is involved in OA pathogenesis. This study investigated the effects of BAI on IL-1β-induced ferroptosis in OACs and explored its underlying mechanism. BAI significantly reduced IL-1β-induced intracellular Fe²⁺ accumulation, mitochondrial dysfunction, and ferroptosis-related protein expression (GPX4, SLC7A11, P53, ACSL4), as well as oxidative stress markers (ROS, LPO, MDA). It also reversed IL-1β-induced decreases in Collagen II and increases in MMP13, and attenuated IL-1β-induced cytotoxicity. BAI activated the Nrf2 antioxidant system, which is crucial for protecting CHs from ferroptosis. When Nrf2 was knocked down using siRNA, the protective effects of BAI were significantly reduced, indicating that Nrf2 activation is essential for BAI's protective role. The study demonstrated that IL-1β induces ferroptosis in CHs, and BAI inhibits this process by activating the Nrf2 pathway, thereby reducing intracellular ROS and lipid ROS accumulation. BAI also inhibited IL-1β-induced ECM degradation and protected CHs from ferroptosis-induced damage. These findings suggest that BAI may be a potential therapeutic agent for OA by targeting ferroptosis in CHs. The results highlight the importance of the Nrf2 pathway in protecting CHs from ferroptosis and provide a basis for developing new treatments for OA.Baicalin (BAI) inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes (OACs) by activating the Nrf2 signaling pathway. Osteoarthritis (OA) is a degenerative disease involving articular cartilage, with chondrocytes (CHs) playing a key role in its progression. Ferroptosis, a type of iron-dependent cell death, is involved in OA pathogenesis. This study investigated the effects of BAI on IL-1β-induced ferroptosis in OACs and explored its underlying mechanism. BAI significantly reduced IL-1β-induced intracellular Fe²⁺ accumulation, mitochondrial dysfunction, and ferroptosis-related protein expression (GPX4, SLC7A11, P53, ACSL4), as well as oxidative stress markers (ROS, LPO, MDA). It also reversed IL-1β-induced decreases in Collagen II and increases in MMP13, and attenuated IL-1β-induced cytotoxicity. BAI activated the Nrf2 antioxidant system, which is crucial for protecting CHs from ferroptosis. When Nrf2 was knocked down using siRNA, the protective effects of BAI were significantly reduced, indicating that Nrf2 activation is essential for BAI's protective role. The study demonstrated that IL-1β induces ferroptosis in CHs, and BAI inhibits this process by activating the Nrf2 pathway, thereby reducing intracellular ROS and lipid ROS accumulation. BAI also inhibited IL-1β-induced ECM degradation and protected CHs from ferroptosis-induced damage. These findings suggest that BAI may be a potential therapeutic agent for OA by targeting ferroptosis in CHs. The results highlight the importance of the Nrf2 pathway in protecting CHs from ferroptosis and provide a basis for developing new treatments for OA.