Ovarian cancer is the most aggressive type of gynecological cancer. The cause of the poor survival rate is the development of chemotherapy resistance to platinum-based therapies, including cisplatin. The present study aimed to investigate the mechanism of cancerous inhibitor of protein phosphatase 2A (CIP2A)-induced chemoresistance in ovarian cancer. The present study initially investigated the expression of CIP2A in the ovarian tumor tissue, cisplatin-sensitive SKOV-3 cell line, and cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line. In addition, CIP2A was knocked down using small interference RNA in ovarian cancer cells and the chemosensitivity of these cells was analyzed. The results demonstrated that CIP2A expression was significantly higher in patients with ovarian cancer and in the cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line at the mRNA and protein levels. The proliferation and chemosensitivity were decreased and enhanced, respectively, when CIP2A was knocked down. CIP2A silencing significantly promoted the apoptosis induced by cisplatin in SKOV-3CDDP/R cells, suggesting that CIP2A participated in the cisplatin resistance of ovarian cancer cells and that CIP2A silencing enhanced the apoptosis induced by cisplatin. CIP2A may be considered as a potential candidate for modulating cisplatin therapy in ovarian cancer.