FMS-like tyrosine kinase 3 (FLT3) plays a very important role in regulating the proliferation, differentiation and survival of normal hematopoietic stem cells. Internal tandem duplications of the FLT3 gene (FLT3-ITD) mutations are present in 25% of all acute myeloid leukemia (AML) patients and are frequently associated with adverse clinical outcomes. Therefore, FLT3-ITD is a promising target for the treatment of AML. The use of covalent virtual screenings has shown that efficient rational approaches for the rapid discovery of new drugs scaffold. Herein, we report a hybrid virtual screening strategy that led to the discovery of FLT3 inhibitors. Using the combination of non-covalent docking and covalent docking, 8 compounds were found to inhibit FLT3, and G856-8335, S346-0154 are also effective against mutant FLT3. These two compounds also show selectivity to receptor tyrosine kinase (C-KIT), which has the potential for optimization. And this work can be extended to the screening of other covalent inhibitors.