Cancer isone of the global health problems and the most frightening and fatal disease of human. With rapid development of nanotechnology, nanocomposites were used to improve antitumor therapeutic efficiency. Chitosan CS possesses many biological functions including antitumor due to its nontoxicity, biocompatibility and biodegradability. The aim of the present work is modification of CS with furanone derivatives 3A or3B to give CS-I and CS-II derivatives respectively using microwave-assistant as a green technique to enhance the antitumor properties of CS. Nanocomposites were prepared by assembling Au, Ag orZnO NPs on CS-I and CS-II derivatives. Structures of CS-I, CS-II derivatives and its nanocomposites were confirmed using different spectroscopic tools. The antitumor efficiency was assayed against two kinds of cancer cells HepG-2 hepatocellular cancer and MCF-7 breast cancer. CS-I and CS-II derivatives revealed significant decrease in cancer cells viability reached to 13.69±2.03% and 10.54±0.92% against HepG-2 respectively and 16.85±2.13% and 11.39±0.97% against MCF-7 respectively compared to 25.48±1.66% and 26.76±1.96% for CS respectively. Additionally, nanocomposites showed superior cell viability and CS-I ZnONPs and CS-I Ag NPs derivatives showed the lowest value reached to 4.84±0.51% and 5.41±0.63% against HepG-2andMCF-7 respectively. It was indicated that the new modified CS derivatives and its nanocomposites could be served as potential anticancer agents.