Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression VEGF and HIF-1α. The VEGF and HIF-1α has intervene in the renal cell carcinoma angiogenesis and metastasis. In this study, we assayed the cell viability, cell invasion/migration, matrix metalloproteinases(MMPs) activity, and urokinase-plasminogen activator (u-PA) activity of 786-O cells with silibinin treatments by MTT assays, invasion/motility assays, gelatin、casein zymography. We found that silibinin relevant to inhibite the cell invasion/migration capacities and the activities of MMP-2, MMP-9 and u-PA in VHL-null 786-O ccRCC cells. without affecting cell viability. Besides, we showed that silibinin downregulated the protein of MMP-2, MMP-9 and u-PA, and also enhanced expression of TIMP-2 and PAI-1. A treatment with silibinin also led to a dose-dependent inhibition on the activation of ERK1/2, p38, NF-κB, c-Jun and c-Fos. In vivo, an anti-tumor study using nude mice (ICR nu/nu) xenograft model by a subcutaneous inoculation of 786-O cells was performed. The average tumor volume of treatment groups was lower than that of control group, statistically. In conclusion, silibinin may be a powerful candidate for a preventive agent against kindey cancer development and metastasis. On the other hand, we investigated the activity and toxicity of a combination of taxol, vinorelbine(VBL) and 5-fluorouracil(5-FU) in metastatic renal cancer. We found that silibinin with low concentration of anticancer drugs have the similar death rate of the high concentration. Among these anticancer drugs, 5-fluorouracil had a best effect upon inhibit the cell viability. These results suggest silibinin in combination with anticancer drugs may be a beneficial chemotherapeutic strategy. This review focuses on the chemistry and analogues of silibinin, multiple possible molecular mechanisms, in vitro as well as in vivo anti-cancer activities, and studies on human clinical trials.