Ninety-six genes showed salient centrality within the PIM mediating the tumorigenesis of OTSCC and BSCC, in which EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, and HSPA5 were significantly linked to a poor prognosis in HNSCC. This evidence concerns the gene CYCS and head and neck squamous cell carcinoma.