Daphne genkwa root has been traditionally used as an effective remedy to treat various tumors. However, the active constituents for its antitumor potency have not been well documented. During the screening for antitumor constituents, it was found that daphnodorins were responsible for the inhibition of tumor growth and metastasis. In this study, six daphnodorins including daphnodorins B (1), G (2), H (3), H-3''-methylether (4), H-3-methylether (5) and G-3''-methylether (6) were investigated for the protection against LLC-induced reduction of lymphoid organs and peripheral lymphocytes, and for the activities against tumor growth and metastasis. The six daphnodorins showed selective cytotoxicity to a number of tumor cell lines. Treatment of LLC-bearing mice with daphnodorin B and/or daphnodorin complex evidently protected peripheral lymphocytes from tumor-induced reduction, increased lymphocyte proliferation potential and inhibited tumor progression and metastasis at doses of 40 and 80 mg/kg. These results indicated that daphnodorin B or daphnodorin complex inhibited tumor growth and metastasis by protecting host immunocyte viability and proliferation potential, and selectively inhibiting tumor cell proliferation.