Erythroferrone (ERFE), a regulator of systemic iron homeostasis, has recently been recognized as a novel player in cancer biology, but its role in the tumorigenesis and progression of non–small cell lung cancer (NSCLC) remains unclear. Transcriptome analysis and gene set enrichment analysis (GSEA) of ERFE-high tumors showed enrichment of cell cycle progression and DNA repair pathways. In NSCLC, ERFE overexpression promoted cell proliferation and colony formation whereas knockdown of ERFE suppressed those phenotypes. Moreover, ERFE-overexpressing cells exhibited enhanced resistance to cisplatin, a DNA-damaging chemotherapy, as indicated by increases in cell survival and colony formation, and reduced apoptotic markers. Together, these findings suggest that ERFE contributes to NSCLC growth and chemoresistance, highlighting its potential as a therapeutic target.