Angiogenesis is crucial for cancer growth and metastasis and inhibition of angiogenesis has been recognized to be a promising strategy for the treatment of cancer. Traditional Chinese medicine (TCM) has been used for thousands of years to treat cancer. Jiedu Xiaozheng Yin (JXY), a polyherbal formula of TCM, has been used to treat various tumors in China. However, the mechanism of its anticancer activity has yet to be fully elucidated. Using human umbilical vein endothelial cells (HUVECs), chick chorioallantoic membrane (CAM) and a hepatoma mouse xenograft model, we investigated the underlying molecular mechanisms of ethanol extract of Jiedu Xiaozheng Yin (EE-JXY). EE-JXY treatment significantly inhibited tumor cell growth both in vitro and in the mouse xenograft model (P<0.05). Moreover, EE-JXY reduced tube formation of HUVECs and angiogenesis in the CAM (P<0.01) and microvessel density (MVD) of tumor in vivo (P<0.05). Further studies showed that EE-JXY was able to suppress the expression of vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR-2) in both HepG2 cells and HUVECs (P<0.01) and in tumor (P<0.01). Thus, JXY suppressed tumor growth at least by inhibiting angiogenesis.