The dysregulated E2F1, E2F2, E2F4, E2F5, E2F6, E2F7, and E2F8 expressions were correlated with clinical characteristics including T stage, N stage, clinical stage, gender, age, histologic grade, and smoking, indicating an extensive influence of E2Fs in the genesis and progress of HNSCC. The gene discussed is E2F5; the disease is head and neck squamous cell carcinoma.