Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) null genotypes have been considered risk factors for many cancers. Numerous studies have been conducted to evaluate the association of null genotype of GSTM1 and GSTT1 with increased susceptibility to oral cancers, and these have produced inconsistent and inconclusive results. In the present study, the possible association of oral cancer(OC) with GSTM1 and GSTT1 null genotypes was explored by a meta analysis. A meta-analysis was conducted on published original studies retrieved from the literature using a bibliographic search from two electronic databases: MEDLINE (National library of medicine, USA) and EMBASE. The pooled odds ratio and presence of publication bias in those studies were evaluated. A total of 49 studies concerning oral cancer (OC) were identified for GSTM1 null genotype. Similarly, 36 studies were identified for GSTT1 null genotype. The pooled OR was 1.551(95% confidence interval [CI]: 1.355-1.774) for the GSTM1 null genotype, while for GSTT1 null genotype, the pooled OR was 1.377 (95% CI: 1.155-1.642). No evidence of publication bias was detected among the included studies. The results suggest that the Glutathione S-transferase M1 and Glutathione S-transferase T1 null genotypes significantly enhances the risk of developing oral cancer by a substantial percentage.