Objective: Focal adhesion kinase (FAK) is a tyrosine kinase that belongs to the focal adhesion complex that proved to have a serious role in cancer progression through its upregulation, while proliferating cell nuclear antigen (PCNA) is a proliferation indicating marker that involved in tumors behavior regarding invasiveness. Our aim is to assess the synchronization in the upregualtion of both markers through double immunostaining and their correlation with prognosis worsening in well differentiated and poorly differentiated oral squamous cell carcinoma (OSCC). Study design: A total number of 60 OSCC lesions distributed equally (n= 30) between the first group (well differentiated OSCC) & second group of (poorly differentiated OSCC). Double immunostaining with FAK &PCNA was carried out to determine their localization. Area percent measurement of FAK and nuclear count for PCNA were performed and analyzed. Results: Both area percent measurement of FAK and nuclear count of PCNA are higher in the poorly differentiated OSCC group than that of the well differentiated OSCC group, results showed statistically significant difference between the groups. Conclusion: Our results indicate that both FAK and PCNA are upregulated in poorly differentiated OSCC than in the well differentiated OSCC supporting their role in cancer aggressiveness & progression together with poor prognosis in higher grades of same tumor.