In conclusion, we identified 108 DEGs related to HNSCC metastasis, and constructed a biological signature composed of GNG8, MYO1H, TNFRSF13B, METTL7B, SYT14, and FOXA2 for predicting the prognosis of patients with HNSCC. This evidence concerns the gene TNFRSF13B and head and neck squamous cell carcinoma.