Angiogenesis is an essential process for tumor development and metastasis, therefore inhibition of tumor angiogenesis has become a promising strategy for anticancer treatments. Patrinia scabiosaefolia, a well-known Oriental folk medicine, has been shown to be effective in the clinical treatment of gastrointestinal cancers. However, the precise mechanism of its tumoricidal activity remains largely unknown. Using a colorectal cancer (CRC) mouse xenograft model, the human colon carcinoma cell line HT-29 and human umbilical vein endothelial cells (HUVECs), in the present study we evaluated the effects of an ethanol extract of Patrinia scabiosaefolia (EEPS) on tumor angiogenesis in vivo and in vitro, and investigated the underlying molecular mechanisms. We found that EEPS treatment significantly reduced the tumor volume in CRC mice and decreased the intratumoral microvessel density in tumor tissues. In addition, EEPS inhibited several key processes of angiogenesis, including the proliferation, migration and tube formation of HUVECs. Moreover, EEPS treatment suppressed the expression of VEGF-A in CRC tumors and HT-29 cells. Collectively, our data suggest that Patrinia scabiosaefolia inhibits CRC growth likely via suppression of tumor angiogenesis.