The aim of present work is to improve the solubility, surface charged and capacity of drug loading of graphene oxide (GO) by modification of GO with carboxymethylcellulose (CMC) and Zinc-based metal-organic framework (MOF-5) to realize and control accurately the release manner. To achieve this aim, carboxymethylcellulose/Zinc-based metal-organic framework/graphene oxide bio-nanocomposite (CMC/MOF-5/GO) as a new drug delivery system was synthesized in one-pot through the solvothermal technique. The prepared CMC/MOF-5/GO was characterized and used as a carrier to encapsulate the doxorubicin (DOX) as an anticancer drug. The obtained compounds were characterized using SEM, AFM, XRD, FTIR, EDX spectroscopy, BET and Zeta potentials-DLS analysis. The AFM images of GO and CMC/MOF-5/GO illustrated that the sheet thickness of GO was around 30 nm, which increased to ˜80 nm after modification with CMC and MOF-5.In addition, the drug delivery evaluation showed that the DOX-loaded bio-nanocomposites enhanced anticancer properties. Under tumor cell microenvironment at pH 5, the DOX release rate was significantly higher than that under physiological conditions at pH 7.4. The MTT results showed that DOX@CMC/MOF-5/GO exhibits notable cytotoxicity to K562 cells. The resulted bio-nanocomposite showed that this carrier system could be potentially used in anticancer drug delivery systems.