Lichen planus is a chronic autoimmune multi-factorial inflammatory condition of the mucocutaneous skin that mainly interests the skin and oral mucosa. Oral Lichen Planus (OLP) affects 0.5 to 1% of the world's population and all human races equally. The factors that act as triggers of autoimmune processes and determine the appearance of OLP are represented by genetic predisposition, skin injuries, viral infections, contact allergies, and medications. OLP affects the oral mucosa and occurs frequently on the inside of the cheeks and less often on the edges of the tongue, gums, or lips. The condition is manifested by the appearance of painful erosions and mouth ulcers, accompanied by erythema and gingival scaling, and sometimes localized inflammation of the gums, near the amalgam fillings. There are 132 genes currently involved in the etiopathogenesis of OLP, but only a few appear to play a major role. These genes have been termed "leader genes". Thus, based on bioinformatics studies, the main genes involved in the pathogenesis of OPL are JUN, EGFR, FOS, IL2, and ITGB4. Although genetic status, immune system background, and infectious diseases are considered to be the most important incriminating and determining factors, the etiopathogenesis of OLP remains poorly known. Further genetic research is needed in order to achieve the generalizability of the findings and to strengthen the obtaining results.