Ovarian cancer is the most lethal gynecological cancer type in the United States. The success of current chemotherapies is limited by chemoresistance and side effects. Targeted therapy is a promising future direction for cancer therapy. In the present study, the efficacy of co-targeting IL-6 and IL-8 in human ovarian cancer cells by bazedoxifene (Baze) + SCH527123 (SCH) treatment was examined. ELISA, cell viability, cell proliferation, cell migration, cell invasion, western blotting and peritoneal ovarian tumor mouse model analyses were performed to analyze the expression levels of IL-6 and IL-8, tumor growth, tumor migration and invasion, and the possible pathways of human ovarian cancer cell lines (SKOV3, CAOV3 and OVCAR3) and patient-derived OV75 ovarian cancer cells. Each cell line was treated by monotherapy or combination therapy. The results demonstrated that IL-6 and IL-8 were secreted by human ovarian cancer cell lines. Compared with the DMSO control, the combination of IL-6/glycoprotein 130 inhibitor Baze and IL-8 inhibitor SCH synergistically inhibited cell viability in ovarian cancer cells. Baze + SCH also inhibited cell migration and invasion, suppressed ovarian tumor growth and inhibited STAT3 and AKT phosphorylation, as well as survivin expression. Therefore, co-targeting the IL-6 and IL-8 signaling pathways may be an effective approach for ovarian cancer treatment.