Background: Lung cancer (LC) is the most common cause of cancer-related mortality; it is one of the most important common diseases with complicate, multi-factorial etiology, including interactions between genetic makeup and environmental factors. Individuals may differ in their susceptibility to environmental risk factors. This difference of susceptibility may result from inherited polymorphisms in various genes controlling carcinogen metabolism, repair of DNA damage and cell cycle.Objectives: Glutathione S-transferase (GST) plays a key role in detoxification of carcinogens present in tobacco smoke and consequently polymorphisms in this gene may confer susceptibility to many types of cancer such as lung cancer. In the current study the effect of GSTM1 and GSTP1 polymorphism on the development of lung cancer among Egyptian patients was investigated.Methods: The GSTM1 was analyzed using multiplex polymerase chain reaction (PCR) while polymorphism of GSTP1 was analyzed using RFLP. Results: It was found that there is no significant difference (p value = 0.8) in GSTM1 genotype distribution between control and lung cancer cases as it was absent in 33.3% in control and 31.25% in patients. While GSTP1 single nucleotide polymorphism (SNP) encoding A313G base change increases the susceptibility for lung cancer especially among smokers as odds ratio was 5 in case of smokers carry ile/val or val/val genotypes. Also, combination of GSTP1 and GSTM1 polymorphism increases the risk for lung cancer. Our data may provide additional information to the understanding of the molecular mechanism and individual susceptibility to lung cancer in Egypt.