Further analyses demonstrated that: (i) LIFR-knockout mouse liver progenitor cell lines (PHM) were resistant to ferroptosis, while LIFR overexpression sensitized PHM cells to ferroptosis inducers; (ii) the knockout of LIFR increased p65 phosphorylation in PHM and human liver cancer cell lines; conversely, LIFR overexpression reduced p65 phosphorylation, which was rescued by the knockdown of phosphatase SHP1; and (iii) knockdown of LIFR increased LCN2 levels, conferring resistance to erastin and sorafenib, which could be reversed by knockdown of LCN2. The gene discussed is LIFR; the disease is liver cancer.