Previous evidence indicated that N-acetyltransferase 2 (NAT2) polymorphisms might be a risk factor for several cancers. A number of studies have been conducted on the association between NAT2 polymorphisms and head and neck cancer (HNC) risk. Nevertheless, the results were conflicting. Published meta-analysis on this issue has generated inconclusive results. Thus, we aimed to derive a more precise estimation of the relationship by conducting an updated meta-analysis. Published data prior to August 2013 have been searched and screened. Subgroup analysis on ethnicity, source of controls, sample size, and genotyping method were also performed. As a result, a total of 23 case-control studies including 4,028 cases and 4,872 controls were selected for analysis. Interestingly, the results showed that NAT2 polymorphisms might increase HNC risk for the overall data (OR 1.23, 95% CI 1.01-1.49). Moreover, in subgroup analyses according to ethnicity, data showed that slow acetylators might increase HNC susceptibility among Asians (OR 1.78, 95% CI 1.27-2.49), but not among Caucasians or mixed ethnicities. In conclusion, NAT2 polymorphism might be a low-penetrant risk factor for HNC among Asians.