The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism(rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We firstconducted a case-control study to assess this association in a large Han Chinese population, and then performeda meta-analysis to further address this issue. Although our case-control association study indicated no significantdifference in the genotype and allele distributions of C609T polymorphism between gastric cancer patientsand controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated asignificantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84),dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratifiedanalysis by study design demonstrated stronger associations in population-based than in hospital-based studies.And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 geneC609T polymorphism increases the risk for gastric cancer, especially in Asian populations.