ΔNp63 exerts dominant-negative activities against TAp63 and p53, and ΔNp63 is thus considered as an oncoprotein. The majority of the initial alterations of precancerous and cancerous oral lesions are not readily recognizable, on clinical or histopathological examination. The basic biology of initiation and progression of these tumors is still obscure. So the objective of this study is to evaluate the expression of ΔNP63 among normal oral epithelium, oral carcinoma in situ and OSCC using an immunohistochemical approach. Material and methods: A total of 78 archival paraffin embedded specimens (26 normal oral epithelium, 26 oral carcinoma in situ and 26 OSCC) will be collected. The mean ΔNP63 will be evaluated by immunohistochemical staining, (P < 0.05) was considered statistically significant. RESULTS: ΔNp63 the greatest mean area of immunoexpression was recorded in the poorly differentiated OSCC, whereas the least value was recorded in normal mucosa. (ANOVA) test revealed that the difference was extremely statistically significant (P<0.0001). CONCLUSION: The intensity of positive immunoreaction gradually increased with progression of OSCC.