Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) have been involved in the risk of hepatocellular carcinoma (HCC). However, the interactive effect of GSTM1 and GSTT1 has not been reported previously. The aim of this work was to investigate the interaction and synergism of their variants. We identified nine publications including 1,085 cases and 2,396 controls containing both GSTM1 and GSTT1, and the bi-factor variance analysis of equal repeated test, binary class logistic regression analysis, meta-analysis and probability method were used in this analysis. Data showed there was no interaction between GSTM1 and GSTT1 null genotype variation in HCC development. In addition, individuals with at least one null genotype of GSTM1 and GSTT1 had higher susceptibility to HCC (OR = 2.99, 95 % CI 2.21-4.02). In the control group, the probability of individuals with at least one null genotype of GSTM1 and GSTT1 was 0.6624, while in the case group, the probability to develop HCC with at least one null genotype of GSTM1 and GSTT1 increased to 0.1760, which was considered as the changing characteristics of HCC occurrence in Chinese population. Our result suggests that there would be no direct interaction of GSTM1 and GSTT1 genotype in HCC risk. We speculate that GSTM1 and GSTT1 genotype variations have their own independent function in HCC development and may mutate independently to cause HCC. The synergism variants of the two genes in HCC development have bigger risk in Chinese population.