In this study, we found that, compared with normoxia-derived tumor exosomes, hypoxia-derived tumor exosomes more potently promoted M2 polarization of macrophages and TGF-β1/IL-10 secretion via NADH: ubiquinone oxidoreductase core subunit V2 (NDUFV2), as evidenced by the increased mitochondrial functions, including oxidative phosphorylation, ATP levels and mitochondrial membrane potentials, which collectively suppressed macrophage ferroptosis in an NDUFV2-dependent manner. This evidence concerns the gene NDUFV2 and neoplasm.