In this study, we aimed to conduct a series of bioinformatics analyses to explore the pivotal role of PLEK2 in HNSCC, including comparing the expression level of PLEK2 between tumor tissues and normal tissues, exploring the effect of PLEK2 expression on HNSCC prognosis, investigating the co‐expressed genes of PLEK2 in HNSCC. This evidence concerns the gene PLEK2 and neoplasm.