This research has focused on the incorporation of the thiadiazole moiety into versatile pyridine ring because of their biological properties. In order to explore the possibilities of some altered biological action author envisaged that by designing the Schiff base derivatives of 1, 3, 4-thiadiazole moiety may exhibit anticancer properties. These novel 1,3,4-thiadiazole Schiff base compounds have been synthesized by microwave-assisted synthesis and screened for their cytotoxicity on HeLa, HepG2 and MCF7 cancer cell lines.The key intermediate 2-(4-fluorophenyl)pyridine-3-carboxylic acid was obtained by hydrolysing the ester 3 in presence of KOH and methanol.Thus obtained compound 4 was treated with thiosemicarbazide and phosphorous oxychloride and cyclized in microwave inorder to get the intermediate 5-[2-(4-fluorophenyl) pyridin-3-yl]-1, 3, 4-thiadiazol-2-amine. The amine 5 was reacted with different aldehydes (a-h) in presence of catalytic amount of acetic acid and obtaineda series of novel Schiff base derivatives 6a-6h. These compounds were characterized by MS, 1H-NMR,IR and elemental analysis. Most of the compounds in this series have exhibited moderate cytotoxicity onall the three human cell lines at different concentrations, but two compounds 6f and 6h showed good inhibition towards liver carcinoma cell lines having IC50 of 23.8µMand 13.4µM respectively.