Triazines and its derivatives have attracted considerable attention as cancer chemopreventive agents and also as cancer therapeutics. Many of its derivatives inhibit the growth of human cancer cell lines by triggering apoptosis. With this background, we planned to synthesis a series of triazine derivatives to assess their anti proliferation efficacy on human cancer cell lines. So, 2-(amino) thioxo-3-phenyl-1,2,5,6-tetrahydro-1,2,4-triazine-6-one was prepared via the reaction of (1) N- benzoyl glycine with (2) thiosemicarbazide under fusion at 13°C. Acetylation and (3) alkylation of compound with acetic anhydride and ethyl chloroacetate yielded the corresponding (4) N-acetamide derivative and (5) ethyl N-aminoacetate derivative, respectively. Fused triazo [2,1-a]-1,2,4-triazine-8-ones (6a,b) were prepared from reaction of compound (3) with ω-bromomethyl aryl ketones in presence of fused sodium acetate. Acetylation of compound (6) with acetic anhydride yielded the corresponding N-acetyl derivatives (7a,b). The cytotoxic activities of the 1,2,4-triazine- 6-one derivatives were studied on the tumor cell lines, human colon carcinoma (HCT-116) and human hepatocellular carcinoma cells (HepG-2) using the MTT viability test. The results showed that the investigated compound (6b) had a significantly greater cytotoxic effect compared to that of the other compounds.