Background Lichen planus (LP) is an inflammatory disease that affects skin, hair follicles, mucous membranes, and nails. Ki-67 is an antigen associated with the proliferation of cells in all stages of cell cycle except G0. Bcl-2 is a protooncogene that protects cells from apoptosis. COX-2 is an antiapoptotic protein that increases in inflammation. The infiltration of T cells in LP seems to be responsible in the apoptosis of the basal keratinocytes. Objective The purpose of this study was to investigate the effects of prednisolone and acitretin treatments on Ki-67, Bcl-2, and COX-2 expression and apoptosis in patients with LP and the role of Ki-67, Bcl-2, and COX-2 proteins in LP. Methods Fifty-eight patients with clinically and histopathologically diagnosed LP who had not been treated with systemic treatment before and 15 healthy volunteers were evaluated prospectively. Pretreatment and posttreatment biopsies were immunohistochemically stained with Ki-67, Bcl-2, and COX-2. The percentage of the stained cells were calculated and recorded. Results Although the percentage of staining with Ki-67 and Bcl-2 after treatment with prednisolone and acitretin decreased significantly (P < 0.05) in both groups, there was no significant difference between groups (P > 0.05). COX-2 decreased but was not statistically significant. Conclusions With this study in cutaneous lichen planus, prednisolone and acitretin treatments reduced Bcl-2 and Ki-67 levels and did not effect COX-2 levels. It should be clarified whether these results can be obtained with any treatment effective in cutaneous lichen planus.