In this context, the present study aimed to comprehensively evaluate immunohistochemical expression of p63, Ki-67, SOX2, and E-cadherin; assess serum iron and total protein levels; and analyse ultrasonographic and electromyographic parameters of key masticatory muscles, correlating all findings with the clinical and histopathological grades of OSMF. We hypothesised that aberrant expression of these molecular markers, nutritional deficiencies, and muscle dysfunction is associated with more advanced clinical and histopathological grades of OSMF. This evidence concerns the gene SOX2 and oral submucous fibrosis.