Carcinogenesis is a multistage process involving the activation ofoncogenes and the inactivation of tumour suppressor genes. Cancer results from mutation in the genes which can produce faulty proteins, which in turn results in abnormal cell growth and leads finally to tumour formation.This study was conducted to assess the expression of the antiapoptotic and anti-differentiation protein ΔNp63 and the transcription regulator PCBP1 in oral carcinoma in situ and oral squamous cell carcinoma compared to normal oral epithelial tissue using the immunohistochemical technique. In this study seventy-eight archival specimens were collected and divided into three groups as 26 NOE, 26 OCIS and 26 OSCC. For each specimen three serial sections were cut, these sections were divided into three subgroups stained as follow: the first subgroup prepared forH&E to confirm the previous diagnosis, the second subgroup prepared for immunohistochemical staining using the Biotin-Streptavidin immunoperoxidase technique anti- ΔNP63 antibody: (Novus biological NBP1-29467, USA) and the third subgroup prepared for immunohistochemical staining using the Biotin Streptavidin immunoperoxidase technique anti- PCBP1 antibody: (Novus biological NBP1-80455, USA).Quantification of Δ NP63 and PCBP1 positivity was performed using an image analyser computer system which measured the area percentage of ΔNP63 and PCBP1 immunoreactivity. The positive immunoreactions of ΔNp63&PCBP1 were detected as a brownish colour in the stained tissues.A positive immunoreaction for the ΔNp63 was observed in all specimens of NOE, OCIS and OSCC. In NOE, the immunoreaction was detected in cytoplasm and nuclei of basal and suprabasal cells, while in OCIS cytoplasmic immunoreaction increased to involve the full thickness of epithelium. In OSCC, cytoplasmic immunostaining was seen in malignant epithelial cells, with less prominent nuclear staining. The intensity of positive immunoreaction gradually increased with progression of OSCC.Positive PCBP1 immunoexpression was observed in all studied specimens. In NOE, cytoplasmic and nuclear immunoreaction involved the full thickness of epithelium. Similar findings were noted in OCIS, where the cytoplasmic immunoreaction involved the full thickness of epithelium, with occasional nuclear staining in some epithelial cells. In OSCC, the cytoplasmic immunostaining was seen in most of the malignant epithelial cells, whereas nuclear staining was seen in sporadic manner.Values of the area percent of immunoreactivity was expressed as a mean ± standard deviation. Mean values of different studied lesions were compared using analysis of variance (ANOVA) test using (SPSS 17, statistical package, USA). A P value ˂ 0.05 was considered statistically significant.Regarding ΔNp63 immunoexpression, statistical analysis revealed a significant difference between NOE, OCIS and OSCC, where NOE recorded the least value, while high grade OSCC revealed the highest value.Although the levels of PCBP1 increased with progression of the neoplastic process, ANOVA test revealed that the difference between these levels of immunoexpression was not statistically significant.In conclusion, both ΔNP63 and PCBP1 play a role in normal oral tissue and in the process of malignant transformation.