Previous studies suggest that chemokine CXCL12 and its receptor CXCR4 play important roles in embryonic development, stem cell trafficking, and inflammatory reactions. It is a central factor in directing cell movement of many physiologic and pathologic processes. The mechanisms of cancer cell metastasis and white blood cell trafficking are similar. CXCL12-CXCR4 axis exerts important effects in regulating growth, invasion, metastasis, and secretion of malignant cells. Data from animal experiments suggest that CXCR4 may be an important therapeutic target in inhibiting malignant growth and metastatic behavior of tumor cells. This review focused on the role of CXCL12-CXCR4 axis in regulating tumor metastasis and progression, and the molecular mechanisms that are essential to this process.