Here, we analyzed alternative splicing and mutation of genes in TCGA-HNSCC samples and identified seven potential tumor antigens, including SREBF1, LUC7L3, LAMA5, PCGF3, HNRNPH1, KLC4, and OFD1, which were associated with nonsense-mediated mRNA decay factor expression, overall survival prognosis and the infiltration of antigen-presenting cells. Here, KLC4 is linked to head and neck squamous cell carcinoma.