In summary, our data present isolated XPC c.2815A>C and FAS c.-671A>G SNVs, and for the first time, associations of GSTM1 with XPC c.2815A>C, XPD c.934G>A, XPD c.2251A>C and TP53 c.215G>C, and XPD c.2251A>C with XPF c.2505T>C SNVs, as independent factors for the outcome of HNSCC patients treated with CDD chemoradiation. This evidence concerns the gene ERCC4 and head and neck squamous cell carcinoma.