Cancer is a major public health concern and a leading cause of death worldwide which is exceptionally difficult to cure. Therefore cancer prevention using dietary constituents is an important strategy to reduce and control the incidence of human cancers through host immunomodulation. So, the aim of the present study is to investigate the adverse and prophylactic effect of Active Hexose Correlated Compound (AHCC) mushroom extract on normal and induced submandibular salivary gland neoplasm in Albino rats. AHCC caused no remarkable histomorphologic changes in the normal rat submandibular gland. AHCC pretreatment 2 weeks before induction of submandibular salivary gland neoplasm and continous supplementation throughout the induction period for 34 weeks resulted in milder dysplastic features compared to the induction group. AHCC caused overexpression of submandibular gland & lymph node cytokines Interferon-(IFN-_) and Interleukin-2 (IL-2). So, from the present study, we concluded that AHCC was largely free of adverse effects in the normal rat submandibular gland and showed a prophylactic effect on the induced submandibular salivary gland neoplasm and this role could be performed through enhancing the host tumor immunesurveillance resulting in slowing down of tumor progression.