A series of novel derivatives 6a-6f of 1, 3, 4-oxadiazole compounds have been synthesized and characterized by 1HNMR, 13CNMR, LCMS and elemental analysis. Synthesis of these novel ethanone derivatives have been synthesized by the 4'-fluoro-3-methylbiphenyl-4-carbohydrazide 4. The 4’-fluoro-3-methylbiphenyl-4- carbohydrazide was reacted with various aldehydes (a-f) in presence of a catalytic amount of acetic acid and obtained the novel Schiff base compounds5a-5f. The Schiff base compounds 5a-5f was acetylated by refluxing with acetic anhydride and obtained the corresponding final derivatives 6a-6f. All these compounds were screened for their MTT assay on three human carcinoma cell lines, namely HeLa, HepG2 and Caco-2. The antiproliferative activity of these 1, 3, 4-oxadiazole compounds showed good cytotoxicity on Caco-2 cell line. The standard used for the experiment was 5-Fluorouracil and the cytotoxicity of the synthesized compounds was compared with the cytotoxicity exhibited by the standard. Among the synthesized compounds,6aand 6e showed good cytotoxicity on Caco-2 cell line having IC50 of6.3μM and 4.4μM respectively. Compounds 6a, 6b, 6c and 6f showed mild cytotoxicity on all the three cell lines.