Objective To study the role of Nuclear Receptor Coactivator 5 (NCOA5) on ovarian cancer cells and molecular mechanisms. Methods Ovarian cancer cell lines SKOV-3, A2780, OC3, HO-8910 and normal ovarian epithelial cell line IOSE80 were cultured regularly. Western blot analysis was performed to detect the expression level of NCOA5 protein in each cell line. Ovarian cancer cells SKOV-3 and A2780 with high expression of NCOA5 were selected and divided into si-NC group and si-NCOA5 group, respectively, and transfected with NC siRNA and NCOA5 siRNA, respectively. Boyden assay was used to detect cell invasion ability, Transwell assay was used to detect cell metastasis ability, and Western blot assay was used to detect the expression levels of EMT-related proteins E-cadherin, N-cadherin, vimentin and Slug. Results Western blot results show that the expression of NCOA5 in ovarian cancer cells were significantly increased (P<0.05). The expression of interference NCOA5 significantly inhibited ovarian cancer cell invasion and metastasis (P<0.05), and promoted the expression of EMT-related protein E-Cadherin, inhibited the expression of EMT-related protein N-Cadherin, Vimentin, and Slug protein in cells (P<0.05). Conclusion NCOA5 promotes the metastasis of ovarian cancer invasion and has the potential to be a new type of prognosis of ovarian cancer and the potential for the treatment of molecular targets.