In conclusion, our findings have uncovered a novel mechanism by which the CXCL12-CXCR4 axis is involved in pro-tumor function of TCF12 in HCC, leading to the activation of the MAPK and PI3K-AKT signaling pathways and thereby promoting HCC cell growth, migration and invasion, which provides a novel target and a valuable prognostic marker for HCC. Here, CXCR4 is linked to hepatocellular carcinoma.