Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Thus, there is an emergent need to invest a novel therapeutic for EOC. In this study, we defined ubiquitin-specific protease 14 (USP14) as a therapeutic target for EOC. Western blot was used to evaluate the expression of USP14 in nine fresh EOC tissues and three fresh normal ovarian tissues. The protein level of USP14 was higher in the cancer samples compared with that in the normal ovary tissues. Immunohistochemistry analysis was performed on formalin-fixed paraffin-embedded section of 116 cases of EOCs and indicated that USP14 was significantly associated with clinical pathologic variables. Kaplan-Meier curve showed that high expression of USP14 was related to poor prognosis of EOC patients. Starvation and re-feeding assay was used to imitate cell cycle, suggesting that USP14 played a critical role in SKOV3 cell proliferation. CCK-8 assay showed that SKOV3 cells treated with USP14-shRNA (shUSP14) grew more slowly than control group. Flow cytometry revealed that the reduced expression of USP14 induced the apoptosis of the SKOV3 EOC cells. In summary, our findings suggest that USP14 is involved in the progression of EOC and that it may be a useful target of therapy in EOC.