Protein-bound polysaccharide K (PSK), which is derived from mushrooms belonging to the Basidiomycetes genus, has been clinically used as a biological response modifier (BRM) for the treatment of epithelial cancer patients in Japan and other Asian countries. There are a large number of studies on the biological activities of PSK as regards the activation of immunocompetent cells and the potential cytotoxic effects on epithelial cancer cells. However, only a few studies have been conducted to see the direct cytotoxic effects of PSK on hematological malignant cells. In this study, we investigated whether or not PSK was able to induce cellular apoptosis in hematological malignant cells. PSK was found to inhibit cell growth, and induced subsequent cellular apoptosis in the Burkkit lymphoma cell line (Namalwa), out of 33 hematological malignant cell lines tested. This PSK-induced apoptosis was neutralized by the addition of galactose to the culture medium, whereas apoptosis was augmented by treatment with beta-galactosidase, indicating the inhibitory involvement of galactose in the mechanism of action. These results provide initial evidence of the direct cytotoxic activity of PSK in a hematological malignant cell line, thus encouraging further molecular-level study of PSK-mediated apoptosis in malignant hematological cells.