Background: Oral Lichen Planus (OLP) is a chronic inflammatory mucosal disease, presenting in various clinical forms WHO had regarded OLP as a precancerous conditions in 1978 because of its potential with cancer. Both antigen-specific and nonspecific mechanisms involved in the pathogenesis of OLP. Oral Squamous Cell Carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity representing more than 94% of oral cancer. It occurs in different sites and has many etiological factors. Cyclin Dl is a proto-oncogene which consider as the key protein in the regulation of cell proliferation and its overexpression led to the occurrence and progression of malignant tumors.NF-KB p65 is a member ofNF-kB family of transcription factors that widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival, also plays a major role in inflammation. The aims of this study were to evaluate the immunohistochemical expression of Cyclin D1 & NF-KB p65 in OLP & OSCC & to correlate the expression of the studied markers with the clinicopathological findings and with each other. Materials and Methods: Fifty (50) formalin – fixed, paraffin – embedded blocks of both Oral Lichen Planus (25 cases) & Oral Squamous Cell Carcinoma (25 cases) were collected pro- and retrospectively were included in this study. Hematoxylin & Eosin stain was performed for each block for reassessment of histopathological examination. An immunohistochemical staining was performed using anti Cyclin D1 and anti NF-KB p65 monoclonal antibodies. Results: Of twenty five OLPstudied cases , positive Cyclin D1 & NF-KB p65 expression was found in (84%) and (88%)of the cases respectively. For OSCC ,out of 25 studied cases ,positive Cyclin D1 & NF-KB p65 expression was observe in (88%) and (96%) of cases respectively. Statistically significant correlation between Cyclin D1immuno- reactivity and clinical presentation of OLP was found. Statistically significant correlation of Cyclin D1 immunoreactivity with tumor grade andNF-kBp65 immunoreactivity with tumor stage in OSCC cases was found. Statistically a highly significant correlation between the expression of two studied markers in OLP and OSCC was found. Conclusion: A highly significant correlation was seen regarding the expression of both markers with each other, suggesting their cooperative role in the pathogenesis of OLP and OSCC.