Lichen planus is a common chronic inflammatory mucosal and skin disorder that affects approximately 0.5–4% of the worldwide population, with a malignant transformation rate of 1.4% [
1,
2]. Also, OLP had a higher prevalence among middle-aged females [
3,
4], while it is also rare in children (0.03%) [
5]. Patients often are unaware of their oral condition [
6]. Compared to the cutaneous form of this disease, oral involvement is more frequent and treatment-resistant [
7]. Oral lichen planus (OLP) forms white lines or plaques, erythema, erosion, or blisters that mainly affect the buccal mucosa, tongue, and gums. Lesions are usually bilateral and often appear as a combination of clinical subtypes [
8]. Clinically, OLP contains various forms, including reticular, erosive, papular, atrophic, plaque-like, and bullous presentations [
9]. Reticular and erosive forms are the most common types of oral lichen planus [
10]. According to the studies, OLP could increase the risk of oral squamous cell carcinoma, which is an oral potentially malignant disorder [
11,
12]. A more significant malignant potential has been identified for the atrophic and erosive forms of OLP [
6]. The etiology of OLP disease is still debated. However, the immune-response pathogenesis of this disease has been recognized [
5]. Some studies have indicated intrinsic and extrinsic factors such as dental materials, some medications, stress, liver diseases, hepatitis C virus infection, tobacco, alcohol consumption, and genetic factors that could be involved in OLP susceptibility [
6,
13,
14]. Substantial evidence suggests that OLP is triggered by an antigen that alters keratinocyte antigen expression or unmasking of an antigen, making them susceptible to cell-mediated autoimmune reactions [
15]. Following, it induces the migration of T lymphocytes (mostly CD8+, and some CD4 + cells) into the epithelium and the production of T helper 1 (Th1) cytokines, such as interleukin-2, interferon-gamma and tumor necrosis factor [
16], which determine the keratinocytes apoptosis, mucosal basement membrane destruction and long-term chronicity of the disease [
15,
17]. Cytokines, such as tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine and potent immune system inducer, are thought to play a pivotal role in the development of OLP and other autoimmune and inflammatory diseases [
18]. Elevated serum TNF-α levels have been observed in OLP patients compared to healthy controls [
11]. So far, several single nucleotide polymorphisms (SNPs) within the promoter sequence (-238, -244, -308, -376, -489, -575, -610, -851, -857, -863, -1031) of the TNF-α gene have been reported that affect transcriptional regulation and therefore susceptibility of different diseases [
19,
20]. The SNP that occurs in the regulatory position − 1031, the promoter of the TNF-α gene, is characterized by the substitution of cytosine for thymine [
21]. This polymorphism change could be related to the up-regulation of TNF-α and cause its increase in blood circulation [
19,
21‐
23]. No study has investigated the association of TNF-α -1031 polymorphism with OLP susceptibility and severity in an Iranian population. Therefore, our study aims to address this knowledge gap and explore the potential link between TNF-α gene − 1031 T/C polymorphism and OLP in the Iranian population.