To investigate the effects of alkannin on the apoptosis and phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway in malignant breast cell lines MDA-MB-231 and MCF-7.Methods:MDA-MB-231 and MCF-7 cells were cultured in the complete media containing different concentrations of alkannin(0，0.2，0.4，0.8，and 1.0 mg/mL).The cell viability，apoptosis，and PI3K/Akt expression were determined by CCK-8 assay，Annexin V-FTIC/PI staining-flow cytometry，and western blotting，respectively.Results:Compared with the blank control group(0 mg/mL)，alkannin at a concentration of 0.8 mg/mL and higher significantly inhibited the growth of MDA-MB-231 and MCF-7 cells，and that of 1.0 mg/L demonstrated the best performance.The apoptosis of MDA-MB-231 and MCF-7 cells increased with the rise in alkannin concentration(P<0.05).Compared with the blank control group，alkannin down-regulated the expression of PI3K in MDA-MB-231 and MCF-7 cells(P<0.05).Conclusion:Alkannin may exert the anti-tumor effects on MDA-MB-231 and MCF-7 cells by inhibiting the PI3K/Akt signaling pathway.