gene variability related to carcinogen activation and detoxification may interfere with susceptibility to head and neck cancer. aim: to investigate the relation between gstt1 and gstm1 null polymorphisms and the risk of head and neck squamous cell carcinoma in cigarette smokers. material and method: a case-control study conducted at the sao jose do rio preto medical school, brazil. gstm1 and gstt1 null genotype frequencies were evaluated by multiplex pcr in 45 cigarette smokers with head and neck squamous cell carcinomas and 45 cigarette smokers without this disease. results: the oral cavity was the most prevalent tumor site for squamous cell carcinoma. the gstt1 null genotype was found in 33.3% of the experimental group and 23.3% of the control group (p= 0.311). experimental and control groups had gstm1 null genotype frequencies of 35% and 48.3% (p=0.582). no association between alcohol consumption and gstt1 and gstmi null genotypes was found in these groups (p-values>0.05). there were more men, and alcohol consumption was prevalent in both groups. conclusion: in this study we were unable to show a correlation between gstm1 and gstt1 genotypes and the development of head and neck squamous cell carcinomas in cigarette smokers.