Anew series of novel 1,3,4-oxadiazoles derivatives have been synthesized by linear synthetic method and screened these compounds for anticancer activity on HeLa, MCF7, Caco-2 cell lines. Final 1, 3, 4-oxadiazoles 6a-6f were characterized by LCMS,1H NMR,13C, and elemental analysis. Oxidative cyclisation reaction of the corresponding key intermediate Schiff base derivatives 5a-5f yielded the desired novel 1, 3, 4-oxadiazoles. Most of the compounds in this series showed moderate cytotoxicity on all the cell lines, but compounds 6d and 6f is more cytotoxic on Caco-2 and HeLa cell lines respectively. The standard used was 5-FU and cytotoxicity of the compounds were compared with the 5-FU. The IC50 values of compounds 6d and 6fis 2.4μM and 5.3μM on Caco-2 and HeLa cell lines respectively.