Objective To explore the proliferation-inhibition and inducement of apoptosis efficacy of decoction of Euphorbia fischeriana Steud. and jujuba (DEFSJ) on the human breast cancer cell line MCF-7 and reveal the underlying molecular mechanisms. Methods DEFSJ-containing serum (CS) was prepared via a serum pharmacology method . Cell morphology was observed by optical microscope and transmission electron microscope (TEM). After MCF-7 cells were treated with DEFSJ-CS and LY294002 ( PI3k signaling pathway inhibitor), the CCK-8 method was used to detect proliferation, the apoptosis rate was detected with a flow cytometer, and the expression of PI3k/ Akt signaling pathway and Bcl-2 family-related proteins were detected by immunostaining. Results Morphological changes and typical features of apoptosis were observed by optical microscope and TEM. DEFSJ-CS had a significant inhibitory effect on the proliferation of MCF-7 cells (P< 0. 01), and the inhibitory effect was more significant when combined with LY294002 (P< 0. 05,P<0. 01). Annexin V-FITC/ PI staining result showed that, compared with the negative control group, the apoptosis rate significantly increased with the increase of DEFSJ-CS, and the apoptosis rate was more significant when combined with LY294002. Immunostaining result showed that the protein expression levels of PI3k, p-Akt, p-FoxO3a, and Bcl-2 were down-regulated and the levels of Bax and Bim were up-regulated (P<0. 05, P<0. 01), and p-Akt and p-FoxO3a were down-regulated more significantly after combined treatment with LY294002. Conclusions The PI3k/ Akt signaling pathway is involved in the effect of DEFSJ-CS on proliferation inhibition and inducing apoptosis in MCF-7 cells.