The correlation between SLA2 and tumor immune cell infiltration, immune checkpoint, immune-related genes and immune checkpoint blockade (ICB) was detected, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), pathway enrichment analyses were applied to investigate the potential functions of SLA2. These results provide new insights into the function of SLA2 and new targets for the diagnosis and prognosis of HNSCC. This evidence concerns the gene SLA2 and head and neck squamous cell carcinoma.