A series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives has been designed and synthesized in order to find novel anti-tumor compounds. The structures of all the compounds were confirmed by IR, 1H-NMR, MS and elemental analysis. Their anti-tumor activities against cancer cell lines (HT-1080 and Bel-7402) were tested by the MTT method in vitro. Among them, compound 19 displayed the best anti-tumor activity with IC50 values of 12.3 microM and 6.1 microM against Bel-7402 and HT-1080 cell lines respectively.