Evidence is increasingly emerging about multiple roles for the NAD(P)H quinone oxidoreductase 1 enzyme in cancer. The C609T (rs1800566, Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the variation in enzymatic activity across different populations. NQO1 C609T polymorphism was thoroughly investigated with respect to cancer susceptibility. The results were inconsistent partly due to low sample sizes. The aim of the present work was to perform a meta-analysis to assess association for all common cancer sites separately and in combination.Our meta-analysis involved 92 studies including 21,178 cases and 25,157 controls. Statistical analysis involved individual cancer sites and the combined cancer risk. Association was tested under different genetic models.We found a statistically significant association between the variant T allele and overall cancer risk in the worldwide population (for the TT vs CC model, OR=1.18 (1.07-1.31), P=0.002, I²=36%). Stratified analysis revealed that this association was largely attributed to the Caucasian ethnicity (for the TT vs CC model, OR=1.28 (1.12-1.46), P=0.0002, I²=1%). Stratification by tumour site showed significant association for bladder cancer in the worldwide population (for the TT vs CC model, OR=1.70 (1.17-2.46), P=0.005, I²=0%), and in the Asian population (for the TT vs CC model, 1.48 (1.14-1.93), P=0.003, I²=16%). Positive association was also found for gastric cancer in the worldwide population under the dominant model (OR=1.34 (1.09-1.65), P=0.006, I²=15%).Our results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in cancer.