The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. This evidence concerns the gene TP53 and head and neck squamous cell carcinoma.