Cell division cycle protein 20 (Cdc20) is a member of the cell cyclin family. In the early stage of mitosis, it activates the anaphase-promoting complex (APC) and forms the E3 ubiquitin ligase complex APCCdc20, which destroys key regulators of the cell cycle and promotes mitosis. Cdc20 serves as a target for the spindle checkpoint, ensuring proper chromosome segregation. As an oncoprotein, Cdc20 is highly expressed in a variety of malignant tumors, and Cdc20 overexpression is associated with poor prognosis of these tumors. This review aims to dissect the tumorigenic role of Cdc20 in human malignancies and its targeting strategies.