Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. However, the cause of OLP remains unknown. Current evidence suggests that cell-mediated immunity is involved in the pathogenesis of OLP and it may be regulated by various cytokines and their receptors. Tumor necrosis factor-[alpha] (TNF-[alpha]) is a proinflammatory cytokine which may be involved in the basal keratinocyte apoptosis in OLP lesional epithelium. The present study investigated the expression of TNF-[alpha] in OLP compared with normal oral mucosa. Twenty OLP and 20 control tissue biopsies were sent for histopathologic examination and immunologically stained with antibody to TNF-[alpha]. The results showed that 18 out of 20 OLP cases (90%) showed positive staining to TNF-[alpha]. All of the TNF-[alpha] positive were observed in mononuclear cells, whereas only 7 out of 20 OLP cases (35%) were detected in keratinocytes. Only few mononuclear cells in normal oral mucosa showed TNF-[alpha] positive, while all of the keratinocytes in normal mucosa were TNF-[alpha] negative. However, the number of mononuclear cells positive for TNF-[alpha] and mononuclear cells in lamina propria of OLP were statistically higher than normal oral mucosa (p=0.000). Likewise, the number of keratinocytes positive for TNF-[alpha] of OLP were also statistically higher than that of normal oral mucosa (p=0.004). The number of cells positive for TNF-alpha and mononuclear cells in lamina propria of OLP between atrophi and erosive types were not statistically different. These findings suggest that increased expression of TNF-[alpha] may play an important role in the pathogenesis of OLP