In the present study, we firstly showed that ALI could cause ferroptosis in the human proximal tubular epithelial cell, which could be enhanced by induced mitochondrial iron overload via suppressing Nrf2-HO-1/GPX4 mediated anti-lipid hydroperoxidation system, indicating a new toxic mechanism of action of ALI-induced nephrotoxicity. This evidence concerns the gene NFE2L2 and acute respiratory distress syndrome.