Alveolar epithelial apoptosis and injury induced by oxidative stress in pulmonary diseases have drawn great attention from researchers. Peroxiredoxin 6 (Prdx6), endowed with the activities of both glutathione (GSH) peroxidase and phospholipase A₂ (PLA₂), can effectively fight against oxidative stress and alleviate oxidative stress-induced lung injury, and therefore plays an important role in pulmonary diseases. This review focuses on the structure, function, distribution and expression regulation of Prdx6, and summarizes the role of Prdx6 in pulmonary antioxidant defense and its regulatory mechanism based on experimental studies.