Background: Lichen planus (LP) is a chronic mucocutaneous inflammatory condition characterized by white striations and plaques or erythematous /erosive lesions in the oral cavity. LP has affected about 0.5 -1% of world population. Apart from the potential of autoimmune origin, the WHO classified oral LP (OLP) as a premalignant condition, with an increased risk of developing squamous cell carcinoma of the head and neck (SCCHN). Patients with LP have exhibited a higher susceptibility to other autoimmune diseases (about 25%). Case Presentation: A 51-year-old woman with a history of OLP and concurrent lupus erythematosus, transplanted Liver, and ulcerative colitis was referred to the Oral and Maxillofacial Medicine Department of Tehran Dental Faculty. A noteworthy point in this study, which was not commonly observed in previous reports, was the existence of OLP with three autoimmune diseases. The lichenoid oral ulcers of the patient were managed by modifying her drug regimen under consultation with a physician using systemic and topical corticosteroids, and, finally, cryotherapy. Conclusions: This case, not the first case of autoimmune diseases, illustrates the management of the challenges of an oral lesion accompanying other systemic diseases and highlights the importance of awareness of the oral manifestations of systemic diseases and their side effects. According to previous studies, the response of oral lesions to different treatments is unique, and the patient's lifestyle and his/her other systemic diseases influence the treatment success or failure. The patient's management protocol and its validity can be re-evaluated in future studies as clinical trial projects.