Ovarian cancer is the major cause of death from gynecologic malignancies owing to poor prognosis. Stathmin, a microtubule-destabilizing protein, is expressed in a stage-dependent manner in ovarian cancer. Eribulin is a microtubule dynamics inhibitor used to treat breast cancer and sarcoma. The present study explored the antitumor efficacy of eribulin and the involvement of stathmin in the action of eribulin in ovarian cancers. In a xenograft model of ovarian cancer, eribulin treatment reduced the tumor weight accompanied with an increased level of phosphorylated stathmin, and a decreased expression of proliferating cell nuclear antigen (PCNA). Eribulin abolished the formation of tumor blood vessels with large lumens. In cultured ovarian cancer cell lines, eribulin stimulated stathmin phosphorylation and decreased stathmin protein expression. A protein phosphatase 2A (PP2A) activator FTY720 attenuated the eribulin-induced phosphorylation of stathmin. The levels of PP2A subunits were downregulated by eribulin. SiRNA-mediated stathmin knockdown attenuated the inhibitory effects of eribulin on cell viability. In addition, eribulin enhanced the antiproliferative effects of paclitaxel on ovarian cancer cells, which was accompanied by a decreased stathmin expression. These results suggest that eribulin may suppress ovarian cancer tumorigenesis partly by regulating the stathmin dynamics, and that combined treatment of eribulin with paclitaxel could be useful for ovarian cancer.