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Background: Emerging research has identified the N6‐methyladenosine (m6A) modification and its regulatory enzymes, including methyltransferase 5 (METTL5), as critical players in cancer biology. However, the role of METTL5 in oral squamous cell carcinoma (OSCC) remains poorly understood. Materials and Methods: We conducted a comprehensive study to investigate the expression and implications of METTL5 in OSCC. We recruited 76 OSCC patients to analyze METTL5 mRNA and protein expression using RT‐qPCR and western blot. Additionally, we analyzed METTL5 expression and its correlation with clinical features, patient prognosis, immune cell infiltration, and biological pathways using the TCGA‐HNSCC dataset, which primarily consists of OSCC samples. Results: Our findings revealed significant overexpression of METTL5 in OSCC tissues compared to normal tissues. The high expression of METTL5 is associated with advanced cancer stages, higher tumor grades, nodal metastasis, and poorer patient outcomes, indicating its involvement in cancer progression. In silico functional analysis revealed that METTL5 plays a role in multiple biological pathways, highlighting its importance in cancer biology. Moreover, METTL5 has complex relationships with immune regulatory genes, suggesting its potential role in shaping the tumor immune microenvironment. Conclusion: METTL5 is a promising candidate for the prognosis and therapeutic intervention of OSCC. Its overexpression in cancer tissues, association with clinical features, and intricate links to immune regulatory networks underscore its significance in this malignancy. This study contributes to a deeper understanding of the complex factors influencing OSCC, and provides a foundation for future research and potential clinical applications. [ABSTRACT FROM AUTHOR]