Objective:To study the effect of D-Rhamnose β hederin on the apoptosis of breast cancer cells and its effect on PI3K/AKT signaling pathway to explore its antineoplastic mechanisms. Methods:Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with D-Rhamnose β hederin at different concentrations. Apoptosis rate of MCF-7 and MDA-MB-231 after treated with D-Rhamnose β hederin for 48 h were analyzed by AnnexinV/PI double staining of flow cytometry. Protein expression of PI3K/AKT signaling pathway related molecules after treated with D-Rhamnose β hederin were detected by Western blot. Results:D-Rhamnose β hederin with dosage of 20,30,40 -滋g/ml effectively induced cell apoptosis and the apoptosis rate was increased with the rising concentration. After treatment with 20 -滋g/ml D-Rhamnose β hederin for 48 h,the protein expressions of p-PI3K and p-AKT were decreased,but the total expressions of PI3K and AKT were not significantly changed. Futhermore,PI3K inhibitor LY294002 enhanced D-Rhamnose β hederin-induced apoptosis through inhibition of p-AKT. Conclusion:D-Rhamnose β hederin could effect on the expression of AKT phosphorylation and significantly induce the apoptpsis of breast cancer cells by inhibiting the phosphorylation of PI3K.