Nasopharyngeal carcinoma (NPC) is a serious health problem in Thailand. It is caused by the combined effects of Epstein-Barr virus (EBV), carcinogens and genetic susceptibility. The glutathione S-transferase M1 gene (GSTM1) encodes a phase II enzyme responsible for detoxifying carcinogenic electrophiles. Polymorphic null forms of the gene GSTM1 lack enzyme activity and have been associated with susceptibility to several cancers including NPC. To examine the association between GSTM1 polymorphism and NPC susceptibility in Thais, GSTM1 genotypes (normal and null genotypes) in 78 NPC patients and 145 age-matched healthy controls were determined using PCR assays. Overall, no statistically significant differences were observed in the frequency of GSTM1 genotypes between cases and controls, nor among NPC patients compared on the basis of sex and clinical stage of disease. Carriers with the GSTM1 null genotype had a 2.9-fold increased risk for NPC of WHO type III when compared to those with GSTM1 normal genotype (P < 0.05 with OR =2.9, 95% CI = 1.2-6.8). When cases and controls were categorized into 3 age groups (>40, >45 and >50 years), the frequencies of GSTM1 null genotype in cases the >45 and >50 age groups were significantly different from controls (P < 0.05). In addition, carriers of the GSTM1 null genotype in age groups >45 and >50 years had a 2-fold and 3-fold increased risk for NPC when compared to those with GSTM1 normal genotype (OR = 2.2, 95% CI = 1.1-4.7 and OR = 3.0, 95% CI = 1.2-7.5). We suggest that GSTM1 polymorphism may be associated with NPC susceptibility in Thais, especially for GSTM1 null genotype carriers of age higher than 45 years. The GSTM1 null genotype may be a useful genetic marker for predicting Thai NPC and for screening of early stages of Thai NPC.