N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism ofvarious potential carcinogens. In recent years, a number of studies have been carried out to investigate therelationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populationsfor different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysisto further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studiesinvolving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. Wealso evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparentsignificant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GAvs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-basedcontrols (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast,a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancersusceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95%CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94)and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94).We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associatedwith a decreased risk of cancer and is likely a protective factor against cancer development.