Background: Thiazole ring is one of the most important heterocyclic ring systems due to their wide range of biological activities.Objective: we became interested in synthesizing a new series of thiazole derivatives to investigate their antitumor activity against liver and colon cancer cell lines. Method: A novel series of 5-arylazothiazoles was prepared from 2-(-1-morpholino-1-(2-arylhydrazono)propan-2- ylidene)-hydrazinecarbothioamide by different methods. Results: The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their synthesis by alternative methods. The newly synthesized products were evaluated for their anticancer activities and the results reveal that some derivatives show good to moderate activity against hepatocellular (HepG2) and colorectal (HCT-116) carcinoma cell lines. Moreover, the computational studies using MOE 2014.09 software are in full support of the results in biological activity. Conclusion: A new bioactive series of thiazole ring was synthesized and showed promising activities against hepatocellular (HepG2) and colorectal (HCT-116) carcinoma cell lines.