Oral squamous cell carcinoma (OSCC) represents about 95% of all oral cancers.The development and spread of many tumors including OSCC are driven by cancer stem cells(CSCs).Sex determining region Y-box 2 (SOX2) is considered a functional marker of CSCs, it is a transcription factor coding gene, which is located at chromosomal 3q26.33 region. The present study was carried out to investigate the immunohistochemical expression of SOX2 in OSCC and correlate it's expression in different histological grades as well as the available clinical parameters. Paraffin blocks tumor tissues from 40 cases of OSCC were used to evaluate SOX2 immunohistochemical expression. The findings of the current study revealed that SOX2 expression showed high statistically significant correlation with histological differentiation of OSCC, clinical stages and lymph node metastases. From the findings of the present studysuggested that SOX2 expression may be used as prognostic predictor for OSCC, and may aid in decisions on cancer diagnosis and therapy. Keywords : Oral squamous cell carcinoma (OSCC), Sex determining region Y-box 2 (SOX2).