Purpose: TiS 2-HSA-FA, a nanoagent based on titanium disulfide (TiS 2), human serum albumin (HSA), and folic acid (FA), was synthesized for potential use in synergistic photothermal/radiation therapy for colon cancer. Methods: TiS 2 nanosheets were synthesized through a HSA-assisted exfoliation method and then modified with PEGylated FA. The morphology, size, zeta potential, stability, cellular uptake, cytotoxicity, biodistribution, and in vitro and in vivo biocompatibility of the nanoparticles as well as their suitability for synergistic photothermal/radiation colon cancer therapy were investigated. Results: The as-synthesized TiS 2-HSA-FA nanoparticles showed excellent physiological stability, as well as high absorption values in the near-infrared (NIR) and X-ray regions, giving them superb activity as a photothermal and radiation sensitizer. In vitro and in vivo experiments indicated that TiS 2-HSA-FA showed high tumor targeting selectivity, blood circulation time, biocompatibility, and suitability for synergistic tumor photothermal radiotherapy. Conclusion: A multifunctional nanoplatform based on TiS 2 was developed and found to be potentially suitable for synergistic photothermal/radiation therapy for colon cancer.