Background: Oral carcinoma (OC) remains one of the most difficult malignancies to cure. Hesa-A is anIranian herbal-marine compound that has shown promising anti-tumor properties against various human tumors.However, its mechanism of action remains to be addressed. The present study was conducted to evaluate theeffect of two doses of Hesa-A on mRNA expression of erb\b2 as a main prognosticator tumor marker for OC inan animal model. Materials and Methods: A total of 60 rats were randomly divided into 5 groups of 12 animalseach. Rats in carcinoma groups received 0, 250 and 500mg/kg body weight doses of Hesa-A 3 times a day. Theother two groups were considered as treated and untreated control groups. At the end of the experiment, animalswere sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results showedthat compared to the control group, erb\ b2 was over-expressed ~ 30% in the carcinoma group. After treatmentwith 250mg/kg and 500mg/kg body weight of Hesa-A , erb\b2 levels dropped by 24.1% and 3.4 % respectivelycompared to the control carcinoma group (p<0.01, p<0.0001). Moreover, there was a significant relation betweenerb\ b2 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These dataprovide insight into mechanism(s) by which Hesa-A may improve clinical outcome of oral carcinoma by affectingoncogene erb\b2 expression and suggest Hesa-A as an effective chemotherapeutic agent in treatment of HER+tumors.