Background: Oral lichen planus (OLP) is a chronic T cell-mediated, immunological, mucocutaneous disease with a number of genes and inflammatory mediators implicated in its pathogenesis. Heart shock protein 70 and the proinflammatory mediator TNFα have been predominantly involved in the etiopathogenesis of oral lichen planus. Methods: In this study, the action of 27 commonly used drugs for treating OLP at HSP70 and TNFα were evaluated by molecular docking using Maestro Schrodinger version 10.1. X-ray crystallographic structures of the target proteins, that is, Heat Shock Protein 70 (PDB Code: 6FDT) and tumor necrosis factor alpha-1 (PDB Code: 1TNF) were obtained from Protein Data Bank (PDB). The structures of the ligands (27 drugs) were obtained from PubChem in.sdf format. Using Ligprep, pre-processing of the ligands was done. Extra-precision docking was performed with the prepared protein and the ligands. Results: With respect to HSP70, the highest dock score (−4.768) and glide score (−4.818) were seen with hydroxychloroquine (HCQ), followed by epigallocatechin gallate (green tea), methotrexate, and curcumin. The highest dock (−9.525) and glide score (−9.584) in TNFα were seen in with epigallocatechin gallate, followed by HCQ, dapsone, and methotrexate. Conclusion: The results of the study tend to explain the clinical use of HCQ in recalcitrant and severe cases, as well as the anti-inflammatory property of epigallocatechin gallate. The results of the study open ventures for exploring the in silico behavior of drugs for effective pathological management. K E Y W O R D S heat shock proteins, molecular docking, oral lichen planus, pathogenesis, tumor necrosis factor-alpha 1 | INTRODUC TI ON Oral lichen planus (OLP) is a chronic T cell-mediated, immunological, mucocutaneous disease of unknown etiology. The oral mucosa is commonly involved and may be the only site of involvement. OLP has varied clinical presentation varying from reticular pattern, papules, plaques, erythema, and blisters to erosions affecting buccal mucosa, tongue, and gingiva. 1 Various factors have been hypothesized for initiation and aggravation of OLP. 2 The pathogenesis of OLP involves activation of cytotoxic T cells against the epithelial keratinocytes.