Overall, we did not observe any association of XRCC1 Arg399Gln polymorphisms with HNSCC risk in total population (OR = 0.95, 95% CI: 0.76–1.19 for Gln/Gln vs. Arg/Arg, OR = 1.05, 95% CI: 0.92–1.20 for Arg/Gln vs. Arg/Arg, and OR = 1.03, 95% CI: 0.90–1.18 for Gln/Gln+Arg/Gln vs. Arg/Arg) based on 18 studies including 3917 cases and 4560 controls. The gene discussed is XRCC1; the disease is head and neck squamous cell carcinoma.