Iris nertschinsk has been used generally as a decorative plant. However, it has been almost used as a medicine for therapy on various human diseases. In this study, we demonstrate the anti-tumor effect of Iris nertschinsk on human breast cancer cells. Firstly, we found that Iris nertschinsk dose-dependently induced cell death in human breast cancer cell lines, MCF7 and MDA-MB231. Moreover, phosphorylation of p53 was induced after Iris nertschinsk treatment in MCF7 cells, which has a functional p53, but not in MDA-MB231 cells, which has a dysfunctional p53. We next examined whether Iris nertschinsk induces caspase-dependent cell death. Caspase-7 was cleaved after Iris nertschinsk treatment in MCF7 cells. Interestingly, either caspase-3 or caspase-7 was cleaved in MDA-MB231 cells that p53 had been phosphorylated by Iris nertschinsk treatment, indicating that Iris nertschinsk induces apoptosis through the cleavage of caspase-3, -7 in human breast cancer cell lines, MCF7 and MDA-MB231, but related to the status of p53. Therefore, these results suggest that Iris nertschinsk could be used as a treatment for human breast cancer. This research is supported by National Institute of Agricultural Biotechnology research grant.