N6-methyladenosine (m(6)A) plays crucial roles in a diverse range of physiological and pathological processes, and it is believed that it tremendously promotes neoplasia and progression. However, knowledge of the molecular characteristics of m(6)A modification, its prognostic value, and the infiltration of immune cell populations in head and neck squamous cell carcinoma (HNSCC) is still insufficient. Therefore, a pan-cancer genomic analysis was systematically performed here by examining m(6)A regulators at the molecular level within 33 multiple cancer types, and the correlations between the expression of m(6)A molecules were researched using datasets from The Cancer Genome Atlas (TCGA). Based on the above analysis, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is upregulated in HNSCC and may serve as an independent prognostic factor of overall survival, thus showing potential as a prognostic biomarker in HNSCC. Genetic alteration analyses elucidated the reasons for the abnormal upregulation of IGF2BP2 in HNSCC. As a result, IGF2BP2 was selected for further univariate and multivariate analyses. The functions of the related genes were annotated through gene set enrichment analysis, and the activation states of multiple biological pathways were shown by gene set variation analysis. We found that LRRC59 and STIP1 may act as IGF2BP2-associated genes to have a regulatory function in the m(6)A modification. In addition, we found that the status of immune cell infiltration was correlated with the level of IGF2BP2 gene expression. Our results provide supplementation at the molecular level for epigenetic regulation in HNSCC and insight into effective immunotherapy targets and strategies.