Aim: It was to investigate the efficacy of hydroxytyrosol (HT) as chemopreventive agent on induced hamster buccal pouch (HBP) carcinogenesis. Subjects and Methods: Forty Syrian male hamsters five weeks old, weighing 80-120g, were divided into three groups. GI: 10 animals were left untreated. GII: 10 animals were painted with 0.5% 7, 12-dimethylbenz(a)anthracene (DMBA) in paraffin oil, 3 times a week, for 8 weeks (GIIA) and14 weeks (GIIB). GIII: chemoprevention group, 20 animals in which HT was taken at week before as well as during the application of DMBA, 3 times a week on alternative days, for 8 weeks (GIIIA) and14 weeks (GIIIB). HPB mucosa were excised and trimmed to 1-2 cm average size, then processed for hematoxylin and eosin (H&E) stain and Immunohistochemical (IHC) staining utilizing Bcl-2 and Bak antibodies. Results: Gross observation revealed variable changes in the treated (G (s)), (GII and GIII) compared to that observed in GI. Histopathological findings revealed variations among the treated groups. IHC results regarding Bcl-2 expression revealed variability in the area percentage throughout the used groups. GI, GIIA, GIIB, GIIIA and GIIIB were (6.77٪, 31.58٪, 68.37٪, 16.07٪, 48.81٪) respectively, while IHC results regarding Bak expression revealed variability in the area percentage throughout the used groups. GI, GIIA, GIIB, GIIIA and GIIIB were (45.32%, 28.58%, 10.38%, 19.32%, 38.72%) respectively. Conclusion: HT is considered as a promising chemopreventive agent in decrease the incidence of HBP carcinogenesis in gross observation as well as in histological examination.