Through a variety of bioinformatics analyses, we extracted and analyzed data sets from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), and Gene Expression Profile Interaction Analysis (GEPIA) to analyze the correlation between SLA2 and the prognosis, immune checkpoint, tumor microenvironment (TME) and immune cell infiltration of HNSCC, and to explore its potential oncogenic mechanism. The gene discussed is SLA2; the disease is neoplasm.