The use of herbal medicine is a common practice among Chinese women with breast cancer. Yunzhi (Voriolus versicolor), a substance that is regarded as a biological response modifier, is frequently used. The aim of the present study is to evaluate the anti-proliferative action of Yunzhi, polysaccharide peptide (PSP), on breast cancer cells. Breast cancer cells (MDA-MB-231) were cultured with and without PSP for 7 days. Cell growth at 24, 72, 120 and 168 hours was measured by Cell Proliferation Reagent (WST-1). Cells treated with PSP were found to have a significant reduction in cell proliferation as compared to controls after 72 hours of incubation. This lasted for 168 hours. When the effect of PSP on apoptosis was studied by the TdT-mediated X-dUTP nick end-labeling (TUNEL) assay, we found that PSP had a significant effect upon apoptosis from 24 hours onward. Immunostaining showed that PSP increased p21 expression and decreased cyclin D₁ expression. In conclusion, PSP is effective in inhibiting cell proliferation through apoptosis. The mechanism for the apoptosis may be through up-regulation of p21 and down-regulation of cyclin D₁.