Background & Objective: This immunohistochemical study is to investigate the correlation between p53 & Ki67 and the grade of malignancy of squamous cell carcinoma, to estimate functional behavior of the cancerous cell by Ck17, and to compare the results with the histological grading. Methods & Materials: 64 samples (biopsies) were chosen to check for p53, Ki67 & Ck17 at department of oral histology and pathology between 2002- 2009. Conclusion: There is a strong positive correlation between the degree of malignancy and the signs of cellular atypism (morphological changes) and the immunhistochemical positivity specially p53 and Ki67, and there is a strong negative correlation between the positivity of p53, Ki67 and the plasmolymphatic infiltrate. We must be sure of the correct diagnosis of squamous cell carcinoma by histological and immunohistochemical examination, and attention should be given to use more than one immune reactive.