According to Olink Proximity Extension assay and evidences in vivo and vitro, we revealed that the MSCs secreted multiple cytokines, including CCL2, CCL25, CXCL1, TGF-β and GM-CSF to enhance the CSC-like characteristics in HCC cell, and accelerated the formation of the tumor malignancy via increase the CCA. The gene discussed is CSF2; the disease is cholangiocarcinoma.