The aim of the present study was to investigate the effect of honokiol on induced hamster buccal pouch (HBP) squmase cell carcinoma (SCC). Subjects and methods: Thirty hamsters were used and divided into three group (s) (G (S) ), 10 each. GI (normal) was left untreated, the right HBP in GII were painted with 0.5% DMBA (3times/week/14weeks). GIII was treated as GII, in addition, they received honokiol. After termination of experiment, the hamsters were clinically examined, then, euthanized. After that, HBP was excised and routinely prepared for histological examination using hematoxylin and eosin (H&E) stain to record the histopathological findings and the depth of invasion, and histochemically examination utilizing AgNOR stain and picrosiures red stain as proliferative and invasive marker respectively, to record the mean area percentages for statistical analysis. Results: Gross and histopathological observations revealed variable changes in GIII compared to GII. The statistical analysis results, for the depth of invasion, revealed high significant difference between GII and GIII, with p-value:<0.001. Regarding the AgNOR stain, there was high significant difference between GI and GII and, also, between GII and GIII with p-value: <0.001. The polarizing colors of collagen fibers recorded significant difference between GI and GII, GI and GIII, GII and GIII with p-values: 0.042, 0.200, and: 0.175 respectively. The area fraction of the collagen fibers recorded high significant difference between GI and GII and, also, between GII and GIII with p-values: <0.001 for both. Conclusions: Honokiol significantly inhibited of invasion, proliferative activity and tumor progression in DMBA induced HBP SCCS.