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Objective To explore whether erastin induces apoptosis and to investigate the molecular mechanism in A549 cells. Methods A549 cells were treated with erastin at different concentrations, with or without ROS scavenging agent N-acetyl-L-cysteine (NAC) and with or without apoptosis inhibitor (Z-VAD-FMK). Then iron content was measured with Iron Assay Kit, cell injure and apoptosis with CCK-8 and flow cytometry in A549 cells. Results Erastin induced the increase of iron content and followed by the injury of A549 cells. Erastin further induced apoptosis of A549 cells (P＜0.05), which was inhibited by apoptosis inhibitor Z-VAD-FMK. Erastin induced an increase in peroxides (ROS) then followed by apoptosis(P＜0.05), which was inhibited by the ROS scavenging agent NAC(P＜0.05). Conclusions Erastin has an inhibitory effect on NSCLC A549 by inducing intracellular ROS production, which provides evidences for the pathogenesis, diagnosis and treatment of NSCLC.