Iron is essential to life due to its unusual flexibility in serving as both an electron donor and acceptor. However, free iron can damage tissues by catalyzing the conversion of hydrogen peroxide to free-radical ions that attack lipids, proteins and DNA. Hyperoxia-induced lung injury (HILI) occurs when breathing elevated partial pressure of oxygen (usually > 0.5 atmospheres absolute) for extended periods. A few studies have shown that iron and proteins related to iron metabolism are closely related to HILI, and iron chelation may exert protective effects on HILI. As a rate-limiting enzyme in the degradation of heme, heme oxygenases (HOs) play a crucial role in the iron metabolism. Although some studies have been conducted to investigate the role of HOs in the pathogenesis of HILI, findings still conflict, and HOs of different isoforms may function differently in the pathogenesis of HILI. On the available findings, there might be a beneficial threshold of HO-1 expression in HILI. More studies are required to confirm the above findings and to provide evidence for the clinical treatment of HILI by iron chelation.