Kushen (KS), the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As) and Kushen flavonoids (KS-Fs) are the well characterized components in KS. KS-As have been considered biologically active and developed in China as anticancer drugs. In an effort to screen novel antitumor agents from botanicals, more potent antitumor activities were identified in KS-Fs than in KS-As. KS-Fs were able to inhibit the growth of a panel of tumor cell lines and enhanced the antitumor activities of Taxol in vitro. The antitumor activities of KS-Fs and Kur, a single KS-Fs compound, were demonstrated in murine and xenograft human tumor models. Further, it was shown that KS-Fs and Kur were able to enhance the effect of Taxol to inhibit the growth of H460 and Eca-109 xenograft tumors. In addition, peripheral blood cell counts were not significantly affected in normal mice treated with KS-Fs at 200 mg/kg/day for 2 weeks. These results suggest that KS-Fs may be developed as novel antitumor agents and that the currently marketed KS-As drugs in China may have missed the major antitumor activities in Kushen.