Astragalus polysaccharide (APS), a natural anti-oxidant found in Astragalus membranaceus emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on ovarian cancer (OC) remains unknown. In this study, we tried to elucidate the role and mechanism of APS in ovarian cancer cells. Our results showed that APS treatment suppressed the proliferation and induced apoptosis in OC cells. Afterwards, the miRNA profiles in APS-treated cells were determined by a microarray assay, and whether APS affected OV-90 cells through regulation of miRNA was determined. Among these aberrant miRNAs, miR-27a was selected for further study as its oncogenic roles in various human cancers. Moreover, we found overexpression of miR-27a reversed the anti-proliferation and pro-apoptotic effects of APS on ovarian cancer cells. F-box and WD-40 domain protein 7 (FBXW7), a classical tumor suppressor, was found directly targeted by miR-27a and its translation was suppressed by miR-27a in ovarian cancer cells. Finally, it was also observed that knockdown of FBXW7 by si-FBXW7 reversed the tumor suppressive activity of APS in ovarian cancer cells, which is similar with the effects of miR-27a overexpression. Our findings demonstrate that APS can suppress ovarian cancer cell growth in vitro via miR-27a/FBXW7 axis, and this observation reveals the therapeutic potential of APS for treatment of OC.Copyright 2020 The Author(s).