This activation induced macrophage polarization toward the M2 phenotype, which in turn promoted the growth and stemness of cancer stem cells.<h4>Conclusion</h4>This study demonstrates that GCDCA drives HCC progression by inducing M2-type macrophage polarization via the S1PR2/PI3K/AKT signaling pathway, which subsequently enhances tumor cell stemness. Here, S1PR2 is linked to cancer.