Considering the important function of the ERCC4 protein in DNA repair, we conducted a hospital-based case-control study with 1040 SCCHN patients and 1046 controls in a non-Hispanic white population to test the hypothesis that common [minor allele frequency (MAF) ≥5%), potentially functional SNPs in ERCC4 may contribute to the risk of SCCHN. Here, ERCC4 is linked to head and neck squamous cell carcinoma.