The research confirmed that notch1, notch2, Jagged1, Jagged2, DLL1 and DLL4 were over-expressed in RCC CSCs, and blockage of Notch1 or notch2 using pharmacological inhibitor MRK-003 or its endogenous inhibitor Numb resulted in partial loss of its stemness features: self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis in vivo. This evidence concerns the gene DLL4 and renal cell carcinoma.