The flower of Hosta plantaginea (Lam.) Aschers (Liliaceae) is a traditional medicinal material in Mongolian medicine for treating sore throat, hoarseness, pulmonary fever, and toxic fever in folk. The present work investigated anti-prostate cancer and hepatoprotective activities of flavonoid derivatives from H. plantaginea (Lam.) Aschers.To isolate and identify the chemicals of H. plantaginea (Lam.) Aschers for anti-prostate cancer and hepatoprotective activities.Active chemicals were isolated and purified from H. plantaginea (Lam.) Aschers by chromatographic methods, and their structures were established on spectroscopic analysis and references. These compounds were evaluated for their anti-prostate cancer activities using the LNCaP prostate cancer cells, and assayed for their hepatoprotective activities on CCl-induced injury of human L-O2 cells, respectively.Four new flavonol-lignan heterodimers (1-4), together with nine known flavonoid derivatives (5-13) were isolated from this plant for the first time. Among them, some compounds exhibited moderate anti-prostate cancer and hepatoprotective activities.Compounds 1, 2, 5, and 6 showed anti-prostate cancer activities using the LNCaP prostate cancer cells with IC values of 17.84, 33.26, 54.13, and 81.55 μg/mL, and compounds 3, 4, 8, and 9 exhibited moderate hepatoprotective activities, respectively. A preliminary structure-activity relation was summarized in this paper.