Abstract: The ubiquitin-proteasome system (UPS) is one of the most important mechanisms of selective protein degradation. Ubiquitination is a highly ordered, multistep enzymatic process carried out by a well-defined systematic ubiquitin pathway, which is necessary in maintaining the appropriate levels and functional activities of various cellular proteins. Abnormality in UPS is highly related to the development and progression of malignant tumors. UbcH10, an E2 protein catalyzing the E3-dependent multiple ubiqutination leading to proteolysis of substrate proteins, is a cell cycle-related protein involved in mitosis completion. UbcH10 can activate Cdc20/APC and plays an important role in cell cycle progression, cell mitosis, and chromosome segregation. Aberrant expression of UbcH10 impairs the spindle assembly checkpoint, potentially inducing chromosomal instability and aneuploidy. UbcH10 is significantly overexpressed in carcinomas of the breast, gastric, ovary, and liver, as well as in glioblastomas. It is also associated with the degree of tumor differentiation and poor prognosis. UbcH10 may act as a novel biomarker and can be a therapeutic target in cancer patients. In the current review, we summarize the most recent data on UbcH10 and its relationship with cancer.