NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence therisk for digestive tract cancer (DTC) in many studies; however, the results remain controversial and ambiguous.We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimationof any associations. Electronic searches were conducted on links between this variant and DTC in severaldatabases through April 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated toestimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias werealso assessed. A total of 21 case-control studies were identified, including 6,198 cases and 7,583 controls. Overall,there was a statistically significant association between the NQO1 C609T polymorphism and DTC risk (TT vs.CC: OR=1.224, 95%CI=1.055-1.421; TT/CT vs. CC: OR=1.195, 95%CI=1.073-1.330; TT vs. CT/CC: OR=1.183,95%CI=1.029-1.359; T vs. C: OR=1.180, 95%CI=1.080-1.290). When stratified for tumor location, the resultsbased on all studies showed the variant allele 609T might have a significantly increased risk of upper digest tractcancer (UGIC), but not colorectal cancer. In the subgroup analysis by ethnicity, we observed a significantly riskfor DTC in Caucasians. For esophageal and gastric cancer, a significantly risk was found in both populations,and for colorectal, a weak risk was observed in Caucasians, but not Asians. This meta-analysis suggested thatthe NQO1 C609T polymorphism may increase the risk of DTC, especially in the upper gastric tract.