Introduction: Lichen planus is an inflammatory disease of skin andoral mucosa. Evidence has accumulated that cytotoxic CD8+ve Tlymphocytes recognize an antigen on lesional keratinocytes and lysethem. Studies suggested that type I interferons could play an importantrole in cytotoxic inflammation in lichen planus. Type I interferonsstimulate the production of several interferon induced proteins includingmyxovirus resistance protein A (MxA protein).The association of lichen planus and chronic hepatitis C is wellestablished with quite variable prevalence rates among differentpopulation. Many authors considered hepatitis C virus (HCV) as apossible antigen for inducing cytotoxic immune response in lichen planus. Aim of the study: To investigate the role of type I interferons in lichenplanus through detection of MxA protein. To compare betweenexpression of MxA protein in HCV+ve and HCV-ve lichen planuspatients in an attempt to clarify the role of HCV in the pathogenesis oflichen planus. Patients and methods: the study included 33 skin biopsies lichen planuspatients and 10 control biopsies. MxA- mRNA was detected by RT-PCR(Reverse-transcription polymerase chain reaction) technique. Detectionof HCV-specific antibodies in the patients serum was done using ELISAtechnique. Results: Our analysis revealed significantly higher level of MxA proteinin all the lichen planus skin biopsies compared to control biopsies. Theexpression was significantly higher in HCV +ve patients than HCV-ve patients. Conclusion: We concluded that type I interferons play a major role inpathogenesis of lichen planus. HCV could induce lichen planus throughincreasing production of type I interferons