Oral and oropharyngeal carcinomas are common cancers in the world. Therefore, for early diagnosis, prognosis, disease progression monitoring and treatment response, cancer biomarkers are identified as signature molecules.: To evaluate and compare the immunohistochemical expression of MCM-5 in oral squamous cell carcinoma (OSCC) between clinical stages and its histopathological grades.Descriptive cross sectional – in vitro study. This study used immunohistochemistry to examine expression of MCM5 protein in 40 specimens of OSCC and evaluated for localization and staining intensity of MCM-5.: Among 40 cases 39 showed positivity of MCM-5 regarding localization, with highly significant (p < 0.001) correlation among all grades (I, II and III) of OSCC. Findings showed, as histopathological grade increased, nuclear expression and immunostaining intensity of MCM-5 also increased.MCM-5 can be promising diagnostic and prognostic markers, as well as potential targets for anticancer therapy.