SphK1 inhibitors have been considered as effective chemotherapeutic agents for the treatment of cancers. In this work, it is aimed to identify potential SphK1 inhibitors by means of virtual screening and docking simulations. Using Schrödinger’s software, 500,000 compounds from the ZINC database were screened to find their ability to interact with the SphK1 sphingosine-binding pocket. Different ligand-based pharmacophore hypotheses were developed by QSAR studies using ChEMBL database. The validity of these hypotheses was tested by their ability to predict the known activity (pIC50) data reported in literature. The compounds that matched with pharmacophore hypotheses were docked and scored. The pharmacophore hypotheses were further analyzed according to ligand efficiency indices. Top hits will be proposed as potential inhibitors of SphK1. This work will provide a guide for future development of inhibitors targeting SphK1.