Background: New treatment modalities are developed with the aim of escalating tumor absorbed dose and simultaneously sparing the normal structures. The use of nanotechnology in cancer treatment offers some possibilities including destroying cancer tumors with minimal damage to healthy tissues. Zinc Oxide nanoparticles (ZnO NPs) are wide band gap semiconductors and seem to have a good effect on increasing the absorbed dose of target volume especially when doped with a high Z element. The aim of this study was to evaluate the effect of ZnO NPs doped with Gadolinium (Gd) on dose enhancement factor by 6MV photon beam irradiation. Materials and Methods: Various concentrations of ZnO NPs doped with 5% Gd were incorporated into PRESAGE composition, the 3D chemical dosimeter. Then by using a UV-Vis spectrophotometer optical density changes and also dose enhancement factor (DEF) were determined. Results: The results of this study showed that by incorporating 500, 1000, 3000 and 4000 µg/ml ZnO NPs doped with Gd into PRESAGE structure the dose enhancement factor of about 1.57, 1.69, 1.78 and 1.82 in a 15 ×15 cm² field size could be found, respectively. Conclusion: The results of this study showed that ZnO NPs doped with Gd could be considered as new compound for increasing the absorbed dose.