It was found that leukoplakia lesions had higher expressions of HLA-E, HLA-G, CircHLA-C, and HLA-DR.<h4>Conclusion</h4>The upregulation of non-classical HLA molecules, particularly HLA-G, HLA-E, and circHLA-C in oral leukoplakia, suggests an immunologic shift, potentially facilitating tumor immune evasion in oral leukoplakic lesions. Here, HLA-E is linked to leukoplakia.