Abstract: Abnormal modification in protein Neddylation is closely related to the occurrence and progression of various tumors. Studies have shown that the level of enzymes participating in Neddylation is higher than that in normal neighboring tissues, so the relationship between Neddylation and cancer has aroused much concern. Neddylation has been considered to be a novel anticancer target. Neddylation inactivation by a first-in-class small molecular inhibitor, MLN4924, induces cell cycle arrest, apoptosis, senescence and autophagy in different tumor cells. MLN4924 also exerts significant anticancer effects by inhibiting tumor angiogenesis and regulating the function of immune cells. In this review, the latest progress of protein Neddylation and tumor cell cycle, apoptosis, senescence, autophagy, angiogenesis and regulation of immunocyte were briefly introduced to provide theoretical reference for the development of antitumor drugs targeting Neddylation.