The N-acetyltransferase 2 gene (NAT2) has been implicated in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between NAT2 polymorphism and HCC risk. Published literatures from PubMed, EMBASE, CNKI, and Wan Fang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies including 1,084 HCC cases and 1,682 controls were identified for the data analysis. The overall result showed that there was no statistically significant association between NAT2 genotypes and HCC risk (slow acetylation vs. rapid/intermediate acetylation: OR01.03, 95% CI 0.86–1.24). In the stratified analyses, NAT2 genotypes were also not significantly associated with HCC risk among both Europeans (OR01.11, 95% CI 0.86–1.43) and East Asians (OR01.01, 95% CI 0.65–1.56). Further subgroup analyses based on the smoking status showed that the effect size was statistically significant among the smokers (OR02.09, 95% CI 1.07–4.09), but not among those who never smoked (OR01.26, 95% CI 0.88–1.82). The present meta-analysis indicated that NAT2 genotypes were not associated with increased risk of HCC among the overall population but increased the risk of HCC among the smokers.