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. Here, E2F2 is linked to head and neck squamous cell carcinoma.