NAD(P)H quinine oxidoreductase 1 (NQO1) enzyme plays a crucial role in the protection against oxidative stress. The polymorphism of NQO1 C609T has been implicated in the development of hepatocellular carcinoma (HCC). However, the findings were inconsistent due to different ethnicity, sample size, and source of controls in individual studies. To better estimate the association of NQO1 C609T polymorphism with HCC risk, we performed a meta-analysis of all currently available studies on the susceptibility to HCC. The meta-analysis included three independent studies with a total of 1, 595 subjects. The association was assessed under five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of HCC (ORT vs. C = 1.47, 95 % CI 1.07-2.00, P OR = 0.016; ORTT vs. CC = 2.06, 95 % CI 1.06-3.98, P OR = 0.032; ORTC vs. CC = 1.33, 95 % CI 1.06-1.67, P OR = 0.012; ORTT + TC vs. CC = 1.46, 95 % CI 1.19-1.81, P OR < 0.001; ORTT vs. CC + TC = 1.62, 95 % CI 1.25-2.09, P OR < 0.001). Stratified analyses in Asians and hospital-based case-control studies further demonstrated the significant correlation. Sensitivity analysis confirmed the reliability of these findings. Our study firstly shows that individuals carrying the NQO1 C609T variant allele and genotypes are more susceptible to HCC, particularly for Asians.