Purpose: The study was designed to assess the effect of Ki-67 on oral squamous cell carcinoma (OSCC) with the correlation of biomarker level and grades of OSCC. Material and methods: 26 samples (life biopsies) were inspected in this study, 20 of them are OSCC and 6 are normal. The specimens were processed by the routine histological procedure to prepare them for histopathological and immuno-histochemical examinations. Antibodies expression with anti-Ki-67 antibody was evaluated using image analysis for area percentage with the Leica Q550 image analyzer computer system. Statistical analysis was performed using ANOVA test. Results: Histopathological examination of oral squamous cell carcinoma revealed variable dysplastic changes and alterations of the cells. Ki-67 staining of the poorly differentiated group showed higher immuno-expression than both moderately and well-differentiated groups. The negative expression reveled in control group. The marker positive in cells with OSCC and they were found in the periphery more than the center of the tumor nests, where frequent mitoses were observed. Significant differences were recorded between the control group and all of the experimental groups in Ki-67 expression amounts that represent the area percentage of proliferative cells. Conclusion: Ki-67 is a reliable proliferative marker which can be used for the diagnosis and grading of OSCC transformation.