The XRCC1 Arg194Trp and Arg280His polymorphisms are likely to be implicated with the development of head and neck cancer. However, studies of association have been inconsistent. This meta-analysis of the available literature was performed to make a more precise estimation of the risk associated with these polymorphisms. A comprehensive literature search was conducted to identify all case-control studies of the XRCC1 Arg194Trp and Arg280His polymorphisms in head and neck cancer. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 20 eligible studies were selected for this meta-analysis, including 3,362 cases and 5,796 controls for the XRCC1 Arg194Trp polymorphism and 1,932 cases and 2,757 controls for the XRCC1 Arg280His polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg194Trp and Arg280His polymorphisms. When stratified by ethnicity, significant associations were found for Arg194Trp polymorphism in CT vs CC (OR = 1.26, 95% CI = 1.05-1.52) and the recessive model (OR = 1.28, 95% CI = 1.07-1.53) in Asian population, and no significant associations were found in non-Asian population in all genetic models. This meta-analysis suggests that the XRCC1 Arg194Trp polymorphism is a risk factor for head and neck cancer in Asian populations.