Objectives Lung cancer is a disease characterized by uncontrolled cell growth in the lung tissues. The most common causes of lung cancer include smoking, exposure to radon gas, asbestos, environmental pollutants as well as genetic factors. Nitric oxide (NO) has potential mutagenic and carcinogenic activity and may play an important role in lung cancer. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS), inhibits apoptosis and promotes angiogenesis and tumor cell proliferation. The aim of the present study was to examine the possible relationship between eNOS gene intron 4 variable number of tandem repeat (VNTR) and exon 7-G894T (Glu298Asp)polymorphisms and lung cancer risk. Methods DNA was extracted from peripheral blood leukocytes of 107 lung cancer patients and 100 control subjects. Designated polymorphisms were identified by polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP). Results Our study showed that the frequencies of theb/bgenotype andballele of eNOS gene intron 4 VNTR polymorphism were significantly higher in lung cancer patients than in controls (P < 0.05). However, there was no significant association betweeneNOS gene G894Tpolymorphism and lung cancer risk (P > 0.05). Conclusion These results suggest that the presence of the intron 4 VNTR*ballele andb/bgenotype may be a genetic risk factor for development of lung cancer. Further larger-scale studies are needed to confirm these findings.