Context Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma with poor prognosis and high recurrence rates in patients. The development of MCL is largely attributed to cell cycle dysregulation. Cell division cycle 20 (CDC20) is a key member of cell cycle checkpoints, and high expression of CDC20 was reported in a variety of tumors. Few studies have explored the role of CDC20 in MCL. Objective This study was aimed to investigate whether CDC20 could promote cancer progression and the potential of CDC20 to be a therapeutic target in MCL. Design Peripheral blood mononuclear cells (PBMCs) from 18 MCL patients and 7 healthy donors and 5 MCL cell lines (Jeko, Mino, Rec1, Z138, and JVM2) were acquired to detect CDC20 expression. CDC20 inhibitor apcin was used in Z138 to evaluate its antitumor effects in vitro, including cell viability, cell apoptosis, cell cycle, cell migration, and invasion. Possible changes of some related genes were assessed after apcin treatment. Results CDC20 was overexpressed in 94.4% (17/18) of MCL patients and 5 MCL cell lines compared with healthy controls. Cell growth was inhibited, and cell apoptosis was induced in apcin-treated Z138 cells. After 48 h apcin treatment, cell cycle was arrested in the G2/M phase, characterized by an increased number of Z138 cells in this period. The abilities of cell migration and invasion were significantly attenuated with apcin treatment. The expression of cyclinB1, a marker of the G2/M phase, was significantly increased, together with increased Bim expression and decreased Bcl-xL expression in apcin-treated Z138 cells. Conclusions CDC20 might contribute to tumorigenesis in MCL. Further studies should be carried out to determine whether CDC20 inhibitors could impede tumor progression in MCL patients. This work was supported by grants from the Natural Science Foundation of Beijing Municipality [7182178].