Abstract: Sphingosine kinase 1 (SphK1) is an important protein that regulates the lipid microenvironment of cell membranes, and plays an important role in the dynamic equilibrium of ceramide, sphingosine and sphingosine-1-phosphate.The overexpression of SphK1 is closely related to the occurrence, development and migration of tumors as well as the generation of drug resistance.SphK1 inhibitors can induce apoptosis of various tumor cells and reverse drug resistance, which has a good prospect for drug development.In this article, the structural biology of SphK1, the structural types and structure-activity relationships of SphK1 inhibitors are reviewed.