In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Arg/Gln genotype for HNSCC in Caucasians (OR = 1.20, 95% CI: 1.00–1.44) and Gln/Gln genotype for larynx squamous cell carcinoma (OR = 1.63, 95% CI: 1.10–2.40). This evidence concerns the gene XRCC1 and head and neck squamous cell carcinoma.