Abstract: The enzyme thymidine phosphorylase (TPase) is involved in the metabolism of thymidine. It catalyses the phosphorolysis of several nucleoside analogues serving as antiviral or antitumour agents. Besides, it also plays an important role in the angiogenesis. Thus, inhibition of TPase activity may serve as a plausible therapeutic strategy for the treatment of cancer. In this report, the structure-based design, synthesis, and anti-TPase activity of a class of novel inhibitors of TPase are described using fused bicyclic 1,3,5-triazine-2,4-dione or 1,3,5-triazine-2-thioxo-4-one as the core scaffold, and the latter scaffold shows some activity in TPase enzyme assay.