The binding complex of chemokine receptor CXCR4 and its specific ligand CXCL12 triggers the downstream signaling pathway to form biological axis of CXCR4/CXCL12. The axis plays an important role in homing, repopulation of hematopoietic stem cells, as well as maintenance of normal hematopoiesis and homeostasis of hematopoietic microenvironment. Meanwhile, CXCR4/CXCL12 axis is also closely related with relapsed leukemia, since it may promote survival, proliferation, metastasis and drug resistance in leukemic cells.The expression level of CXCR4 could be treated as an important marker for predicting prognosis in patients wizh leukemia, therefore, the combination of CXCR4 inhibitors with routine chemotherapy may represent a powerful approach for the treatment of leukemia.