Biocompatible cross-linked chitosan nanoparticles comprising the cancer chemotherapeutic drug (mitoxantrone, MX) and the novel radiosensitizer hexagonal gold nanoparticles (HG) were prepared and characterized. The prepared nanoparticles were applied, in synergism with external γ-radiation, as dual (chemo-radio) model for treatment of human breast cancer cell (MCF-7). In vitro studies revealed that HG significantly enhances the response of MCF-7 to low and moderate doses of γ-radiation (2 and 4 Gy). Cell viability assay demonstrated the synergistic anticancer actions of mitoxantrone chemotherapy and gold-sensitized γ-radiation therapy. The prepared combinatorial model is potential for efficient and safer treatment of MCF7 cancer cells.