We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified from Alnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel immunomodulator, which augments the activation of natural killer (NK) cells, and thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of oregonin against tumor cells, we examined the effectiveness of NK cells and determined that oregonin could increase NK cell cytotoxicity. This was confirmed by MTT assay. In addition, the survival time of C57BL/6 mice were measured by inoculating 816-F10 melanoma cells to mice via intra muscular (i.m.) injection. Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a significant extension of survival time by up to 51.32%, when compared to the control group. Moreover, oregonin significantly reduced the incidence of pulmonary metastasis, which may be developed from 816-F10 melanoma cells. These findings suggest that oregon in may be classified as a new and novel immunomodulator due to its potential antitumor activity.