We explored the biocompatible gold nanoparticles (GNPs) with surface modified by chitosan in the applications of cell's response to X-ray irradiation. Substantial amounts of chitosan modified gold nanoparticles (CS-GNPs) were found to be internalized in cell cytoplasm revealed by transmission electron microscopy. Their in vitro cytotoxicity effects on MGC-803 cells and GES-1 cells were observed at 24, 48 and 72 h. The MTT results showed that CS-GNPs own excellent biocompatibility. The dose enhancement based on CS-GNPs induced the damage of MGC-803 cells under X-ray irradiation, monitored by clonogenic cell survival assay. We also investigated their effects on the survival rates of MGC-803 cells during irradiation for a dose up to 10 Gy using a radio-oncology linear accelerator (6 MeV). The survival fraction of cells incubated with different concentration of CS-GNPs was obviously reduced in comparison with that irradiation alone. The result also revealed an increase of cell inhibition with increasing the concentration of CS-GNPs. In conclusion, CS-GNPs can enhance the cell radiation therapeutic sensitivity, and have potential application in tumor irradiation therapy in near future.