Background: The purpose of the present study was to evaluate the expression of cell adhesion molecules, E-cadherin and β-catenin in different grades of oral squamous cell carcinoma and to assess their role as biomarkers and potential prognosticators in oral carcinogenesis. In the present study, the expression of E-cadherin and β-catenin is evaluated with the help of immunohistochemical examination. Materials and Methods: Biopsies/specimens of all suspected cases of oral squamous cell carcinoma were fixed in 10% neutral buffered formalin solution. Histopathological diagnosis was made on hematoxylin and eosin (H&E) stained sections and typed into different grades of oral squamous cell carcinoma.The expression of E-cadherin and β-catenin is assessed by immunohistochemistry. Results: In the present study, a total of 71 cases (35 cases of well differentiated squamous cell carcinoma, 25 cases of moderately differentiated squamous cell carcinoma and 11 cases of poorly differentiated squamous cell carcinoma) were subjected to E-cadherin and β-catenin immunostaining. E-cadherin immunohistochemistry showed high immunoreactivity in 91.43 % cases, and low immunoreactivity in only 8.57% cases. β-catenin immunoreactivity was high in 77.14% cases of well differentiated carcinoma and low in 22.86% cases. Conclusion: The suppression of E-cadherin and β-catenin expression is considered as one of the main molecular events responsible for dysfunction in cell-cell adhesion, which leads to local invasion and ultimately tumor development.