Oral lichen planus (OLP) is a chronic inflammatory condition with an unclear etiology. Even though the World Health Organization (WHO) defines OLP as a precancerous condition, the reasons that trigger cancer progression in OLP lesions remain unknown. Cyclooxygenase-2 (COX-2) is an essential enzyme for inflammatory processes and cell proliferation that has been discovered to be overexpressed in OLP lesions in this chronic inflammatory state. The purpose of present research was to determine COX-2 expression levels in histologically identified OLP samples and to correlate it with clinical and histological characteristics. Present study included 30 histopathologically confirmed Oral Lichen Planus lesions. Immunohistochemistry was used to detect COX-2 protein expression. COX-2 expression was compared to certain clinical and histological parameters. The (SPSS) program version (20.0) was utilized to find the relationships between COX-2 expression and these parameters. A Pearson’s correlation between age and sex groups revealed that studies of various age groups revealed a comparable gender distribution with a significant link (P = 0.017). OLP lesions are most commonly found in the buccal mucosa. There is a significant decrease in COX-2 expression was detected in all studied cases of the study. The level of the COX-2 expression rise in correlation with clinical manifestations and cancer development. Through inflammatory reactions, COX-2 is associated with epithelium damage and carcinogenesis pathways.