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<h4>Background</h4>To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.<h4>Methods</h4>We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.<h4>Results</h4>Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80-1.13, P = 0.550, P(heterogeneity) = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99-1.24, P = 0.065, P(heterogeneity) = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97-1.19, P = 0.189, P(heterogeneity) = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68-1.10, P = 0.243, P(heterogeneity) = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.<h4>Conclusions</h4>This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.