In conclusion, we provide evidence in the current study that, macrophage‐derived xCT is involved in regulating TAM ferroptosis and polarization in HCC models and confirm that targeting macrophage‐derived xCT is sufficient to promote tumor development and metastasis, which is achieved by inducing ferroptosis and enhancing its activity in macrophages, as well as diminishing TAM recruitment and infiltration, particularly the M2 polarization. This evidence concerns the gene SLC7A11 and neoplasm.