Results: Using univariate, LASSO, and multivariate cox regression analyses, we developed a prognostic risk model for HNSCC based on 13 genes associated with inflammatory factors (ITGA5, OLR1, CCL5, CXCL8, IL1A, SLC7A2, SCN1B, RGS16, TNFRSF9, PDE4B, NPFFR2, OSM, ROS1). This evidence concerns the gene NPFFR2 and head and neck squamous cell carcinoma.