Abstract Oral lichen planus (OLP), an immune-mediated disorder, has been reported as an extra-hepatic manifestation of Hepatitis C virus (HCV) infection, especially in HCV hyperendemic areas such as southern Europe and Japan. The aim of this study was to investigate from an epidemiological standpoint whether HCV infection is an important factor affecting the relative risk of OLP in a Mediterranean population or whether this relates to the degree of HCV endemicity. Two cohorts of OLP patients resident in two different regions of southern Italy (Campania and Sicily; n = 859) were evaluated for HCV infection status and categorized into five age classes to respective region-matched controls. No significant difference was found between OLP patients and the general population in this area, when data were corrected by the age-stratified prevalence of HCV. Therefore, the age-specific prevalence of HCV infection in OLP patients shows a close trend of direct association with increasing age, without significant differences with the general population of each geographical area. An aetiological link between OLP and HCV cannot be inferred solely by epidemiological data.