BACKGROUND AND AIMS: Ferroptosis plays an essential role in chronic liver diseases, and cyclooxygenase-2 (COX-2) affects liver fibrosis through multiple mechanisms. However, research on COX-2 regulation of ferroptosis in chronic liver injury remains limited. This study aimed to investigate whether and how COX-2 regulates ferroptosis in chronic liver injury. RESULTS: TAA-treated CONCLUSIONS: Ferroptosis contributes to the progression of chronic liver injury. Inhibition of COX-2 upregulates Nrf2, mitigating hepatocyte ferroptosis in chronic liver injury.