Introduction: Carcinogenesis is a multistep process and individual risk to development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on genetic susceptibility of an individual. In head and neck cancer, tobacco exposure and alcohol consumption are predominantly the most significant external factors for tumor formation. Individual’s susceptibility to cancer may be partly explained by variability in enzymatic activities of metabolic genes. Mutations in genes concerned with production of enzymes for metabolism of tobacco products may lead to increased risk of carcinogenesis with respect to oral mucosa. Therefore variations in the expression of these genes due to heritable genetic polymorphisms might modulate the process of carcinogenesis by altering the exposure levels of tobacco derived carcinogens. Objective: This non systematic review summarizes current data available on the role of environment gene interaction in form of GSTM1 null polymorphism and oral carcinogenesis. Literature review: Relevant data was selected in order to summarize the studies conducted on GSTM1 null polymorphism and oral cancer. Conclusion: Relationship between GSTM1 null polymorphism in oral cancer needs to be established to confirm the role of environment gene interaction in oral carcinogenesis.