Background: Oral cancer is one of the most prevalent cancers. Thymoquinone has a potential therapeutic activity against cancer cells. Aim: to compare the effect ofthymoquinone and thymoquinone loaded on gold nanoparticles (GNPs-TQ) as systemic therapeutic agents through intraperitoneal injection for 3&6 weeks after painting of with DMBA 3 times/week for 14w. Material and Methods: This study was carried out on ninety male Syrian golden hamsters (n=90), its age ranged from 6 to 7 weeks, weighting 90-110 gm, purchased from Theodore Blhars Research Institute, Cairo, Egypt. Characterization of GNPs was achieved through using Ultraviolet-Visible spectroscope and transmission electron microscope (TEM). Tissue samples were examined through routine H&E stain, and nuclear factor kappa B cells (NF-κB) immunoreactivity. Results: Formation of spherical and well dispersed gold nanoparticles (GNPs) (27nm). Histopathological evaluation showed retardation of carcinogenesis in hamster buccal pouch and regeneration of striated muscle layers when treated with thymoquinone loaded on gold nanoparticles (GNPs-TQ). These observations were in line with decrease nuclear factor-kappa B expression. Conclusions: GNPs-TQ is a promising chemo-therapeutic agentin regression of carcinogenesis, and improving the general animal health.