Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and is the most lethal gynecologic malignancy. Cytokeratin 19 (CK19) is a small type I cytokeratin. The aim of this study is to explore the functional role of CK19 and its underlying mechanism in EOC.The expression levels of CK19 in EOC tissues were identified by Western blotting and RT-PCR assay. Transwell assay and CCK-8 proliferation assay were used to assess the invasion, migration and proliferation abilities of overexpressed or knockdown CK19 of ovarian cancer cells. We also detected the related genes of Wnt/β-catenin signal pathway, including β-catenin, TCF7, LEF1, c-MYC and cyclin D1 in the transfected ovarian cancer cells by Western blotting and RT-PCR assay.The results demonstrated that CK19 was upregulated in EOC tissue. CK19 was verified to promote the invasion, proliferation and migration of ovarian cancer cells. Additionally, CK19 activates the Wnt/β-catenin signaling pathway by upregulated β-catenin, TCF7, LEF1, c-MYC and cyclin D1.In summary, this is the first study to investigate the role of CK19 in EOC. These findings provide a potential new therapeutic target for the clinical diagnosis and treatment of ovarian cancer.