Objective:To investigate the effect of genistein on the invasion of breast cancer cells (MDA-MB-231) and its possible mechanism. Methods:MDA-MB-231 cells were co-cultured with genistein at various concentrations (25 to 100 μmol/L) for 24 h. Cell invasion ability was studied by Transwell invasion assay. Phosphorylated ERK and total ERK proteins were quantified by Western blot analysis. Distribution of cellular phosphorylated ERK was detected by fluorescence microscope. Intracellular superoxide anion production was stained by DHE staining and detected by fluorescence microscope. Results:After treated with genistein for 24 h,the invasion ability of MDA-MB-231 cells was significantly reduced in a dose-dependent manner compared to the control cells. Consistently,ERK activity and p-ERK location in the nucleus also decreased after genistein treatment. Furthermore,ERK inhibitor U0126 could inhibit cell invasion similarly as genistein. In addition,superoxide anion production was suppressed when treated with genistein,and superoxide anion scavenger TEMPOL could not only suppress ERK phosphorylation,but also inhibit cell invasion. Conclusion:Genistein can inhibit invasive ability of MDA-MB-231 cells,probably through inhibiting the superoxide anion/ERK pathway.