Abstract: Syndecan-1 (SDC1) is one of the main members of heparin sulfate proteoglycan (HSPG), which has functions of regulating metabolism, transporting and information transmission. Heparinase (HPSE) induces the shedding of SDC1, forms the HPSE/SDC1 axis to drive growth factor signal transduction and regulate cell behavior, thereby promoting the growth, metastatic proliferation, angiogenesis and osteolysis of malignant tumors. This paper reviewed the effects of HPSE and SDC1 on malignant tumors, the formation of the HPSE/SDC1 axis and the application of inhibitors targeting the axis in tumor therapy.