Abstract: The aim of the present study was directed to investigate the therapeutic potential of epigallocatechin-3-gallate (EGCG) on cancer stem cell(s) (CSC(s)) of DMBA induced hamster buccal pouch (HBP) carcinoma Material and methods: thirty Syrian male hamsters were divided into three group(s) (G(s)),10 each. GI: negative control, left untreated. The right pouches of those in GII and GII were painted with DMBA (3times /a week/ 14 weeks). GII: positive control, not received other treatment. GIII was injected with intraperitoneally with EGCG. After termination of the experiment, gross observations were recorded, then, the animals were euthanized, all pouches were surgically excised and bisected. The first piece was prepared, fixed and processed for hematoxylin and eosin (H&E) stain examination and immunohistochemical (IHC) staining utilizing CD44 and CD24. The other piece of the fresh tissue was used for flow cytometric (FCM) assessment for identification of CSCs using CD44&CD24 fluorophore-antibodies, then, apoptosis assay of the identified CD44+CD24- CSCs was employed. Results: the results of GIII revealed some variability compared to those observed in GII in gross observations as well as when utilizing H&E stain, CD44 & CD24 IHC and FCM assessment of CSCs. CD44 &CD24 IHC revealed highly significant difference between GII and GIII, (p value > 0.001). CSCs identification, CD44+CD24-& CD44+CD24+revealed highly significant difference between GII and GIII, (p value > 0.05)}. The CD44+CD24- CSCs apoptosis recorded highly significant difference between GII and GIII (p value < 0.001). Conclusion: EGCG significantly inhibits tumor progression and induces apoptosis in CSC of HBP carcinoma.