We hypothesize that combination of tegafur/uracil and thalidomide, both of which have been shown to be active in some HCC patients, may be a highly useful regimen for the treatment of advanced HCC. There are several rationales underlying this combination. First, anti-angiogenesis therapy may improve the efficacy of chemotherapy by normalizing the abnormal vasculature in tumors, and thus improving the delivery of chemotherapeutic agents to the tumor cells. Second, chemotherapeutic drugs given in a low-dose, un-interrupted, and protracted way can induce anti-neoplasm effect through the anti-angiogenesis activity. What so-called "metronomic chemotherapy" is based on direct targeting of the activation, growth, and proliferation of vascular endothelial cells by cytotoxic chemotherapeutic agents. The anti-angiogenesis effect of metronomic chemotherapy is suppressed by VEGF/VEGFR signaling pathways and thus can be further potentiated by agents blocking those survival signals of endothelial cells. In this regard, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models.