In the current study, we observed that the alterations in LPS-induced autophagy enhancement, up-regulation of NCOA4 protein, and down-regulation of FTH1 protein in LPS-induced cells and animal models were attenuated after knockdown of Mir22hg, indicating that Mir22hg might promote ferroptosis by promoting ferritinophagy in sepsis-induced lung injury. The gene discussed is MIR22HG; the disease is Sepsis.