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Background and Objectives: TWIST is a transcription factor that plays a key role in the development of primary tumor to metastatic stage of cancer. It is an inhibitor of E-cadherin in epithelial-to-mesenchymal transformation process (epithelial-mesenchymal transition). Few studies are available on the use of TWIST as a goal in molecular-targeted therapy. The aim of this study was to evaluate of TWIST expression in oral squamous cell carcinoma (OSCC) and its correlation with clinicopathologic factors., Materials and Methods: In this cross-sectional study, immunohistochemical staining was for TWIST performed on 30 paraffin-embedded blocks of OSCC. Furthermore, thirty paraffin-embedded blocks of normal oral mucosa with minimum inflammation from the clinical and histopathologic aspects were selected. Staining intensity and percentage of stained cells from nuclear and cytoplasmic aspects were ranked in epithelial cells. TWIST expression and correlation with clinicopathologic factors were analyzed using Cox regression and Chi-square tests., Results: TWIST expression in OSCC was significantly increased compared to oral normal mucosa. Nuclear expression of TWIST in OSCC was significantly associated with clinical stage (P = 0.01) and lymph node metastasis (P = 0.007). Cytoplasmic expression of TWIST in OSCC was not associated with any clinicopathological factors., Conclusion: The results support the role of TWIST in carcinogenesis, development of OSCC, and its metastasis to lymph nodes., Competing Interests: There are no conflicts of interest