Chemokine CXC ligand 12 (CXCL12)-chemokine receptor 4 (CXCR4) signal axis is involved in the regulation of liver injury repair and the occurrence and development of liver fibrosis. In case of acute and chronic liver injury, the expression of CXCL12 is up-regulated to collect CXCR4-positive immune cells to migrate to the liver. The CXCL12-CXCR4 pathway participates in the occurrence of liver fibrosis by promoting the activation and proliferation of hepatic stellate cells. The emergence of small molecule inhibitors of CXCR4 makes this receptor an attractive target for anti-fibrosis therapy. At present, CXCR4 has been tried as an anti-fibrosis treatment targets for fibrosis of various organs, including pulmonary fibrosis and chronic pancreatitis. However, some studies have shown that simply blocking the CXCL12/CXCR4 axis cannot improve liver fibrosis and even aggravate liver injury. In recent years, with the discovery and understanding of CXCR7, another receptor of CXCR12, the counteracting role of CXCR4-promoting fibrosis pathway and CXCR7-promoting regeneration pathway in liver regeneration and liver fibrosis has been interpreted. Therefore, a full understanding of the regulatory mechanism of CXCL12-CXCR4/CXCR7 pathway, the development of corresponding targeted therapy research for liver disease, and the rebalancing of CXCR4 and CXCR7 are expected to become a new strategy for the liver fibrosis therapy.