Kinesin spindle protein ( KSP) inhibitors is an important direction for the discovery of anticancer agents. Several KSP in-hibitors have been studied in clinic trials. The discovery of ATP-competitive KSP inhibitors may be a new approach for searching novel a-gents to overcome the mutation-mediated resistance to the allosteric inhibitors. The progress in the discovery of ATP-competitive KSP in-hibitors was reviewed in the paper to provide reference for the further development of KSP inhibitors.