Colorectal cancer is highly prevalent worldwide and has significant morbidity and mortality in humans. High-atomic-number nanoparticles such as iodine can act as X-rays absorbers to increase the local dose. The synthesis and fabrication of oxaliplatin-loaded iodine nanoparticles, their characterization, cell toxicity, radiosensitivity, cell apoptosis, and cell cycle assay in human colorectal cancer (HT-29) cells are investigated. Results show that the synthesis of a new iodine nanoparticle, polymerized triiodobenzene coated with chitosan and combined with oxaliplatin as a chemotherapeutic drug, performed well in vitro in an intracellular radiosensitizer as chemoradiotherapy agent in HT-29 cell lines. Findings also show that the INPs alone have no impact on cell cycle development and apoptosis. In contrast, oxaliplatin-loaded INPs along with 2 and 6 MV radiation doses produced more apoptosis. The interaction of INPs with mega-voltage photon energies is the cause of a major radiosensitization enhancement in comparison to radiation alone. Furthermore, results show that INPs may work as radiosensitization nanoprobe agents in the treatment of HT-29 cells due to their effect on increasing radiation dose absorption. Overall, iodine nanoparticles may be used in the treatment of colorectal cancers in clinical studies.