INTRODUCTION: Oral cancer is a major health problem, causing high morbidity and mortality rates. Oral squamous cell carcinoma (OSCC) accounts for 90-95% of all oral malignancies. During the last decade, significant evidence has suggested that inflammation plays an important role in tumorigenesis, and microenvironment-derived signals which are important constituents in all tumors. Toll-like receptors (TLRs) are classical signals that play a key role in the innate immune system. They drive the inflammatory response and control the cellular proliferation and survival by stimulating the immune cells and promoting integrated processes of inflammation and tissue repair. This can predict that TLR4 may be of great significance in tumors. Hence, this study is to evaluate and correlate the expression of TLR-4 in various grades of oral squamous cell carcinoma (OSCC). OBJECTIVES: To evaluate and correlate the expression of TLR-4 in different histopathological grades of OSCC MATERIALS AND METHODS: An immunohistochemical (IHC) study using the TLR-4 antibody were done on 50 surgical specimens and 10 normal mucosal tissues taken from OSCC patients and healthy individuals, respectively. The staining were performed using a Labeled Strept-Avidin Biotin complex method (LSAB) RESULTS: TLR-4 was expressed in human OSCC biopsies and the expression level was correlated with the tumor differentiation. Higher expression was detected in the well and the moderately differentiated squamous cell carcinomas than the poorly differentiated ones. CONCLUSIONS: TLR-4 expression could be a prognostic factor in oral squamous cell carcinoma cases as expression was detected in the well and moderately differentiated higher than poorly differentiated squamous cell carcinomas.