Abstract: This aim of this study is to explore the effect of isorhamnetin on the cell proliferation of breast cancer cells. Two breast cancer cell lines MCF7 and BT549 treated with different concentrations of isorhamnetin were examined for cell proliferation by using MTT assay. The effect of isorhamnetin on cell cycle and apoptosis was determined by flowcytometry. The effect of isorhamnetin on cell proliferation and apoptosis signaling pathway was examined by Western blot analysis. The results showed isorhamnetin can significantly inhibited the proliferation of breast cancer cell lines MCF7 and BT-549, and its IC₅₀ was 11. 72 μmol/L and 8. 74 μmol/L, respectively. Isorhamnetin treatment resulted in cell cycle arrest at G₁ phase and promote apoptosis. Consistent with this finding, isorhamnetin treatment significantly inhibited the AKT and ERK phosphorylation and the expression of proliferating nuclear antigen Ki67. Furthermore, isorhamnetin resulted in the decreased expression of Bcl-2 with concomitant decrease of Bcl-2 expression, subsequently causing the increase of cleaved Caspase-3 and cell apopotosis. Thus, isorhamnetin can significantly inhibit breast cancer cells by both inhibiting cell proliferation and promoting apoptosis.