Stromal cell derived factor-1 (SDF-1), a CXC chemokine that play important roles in tumor growth, angiogenesis and metastasis of tumor cells, has a polymorphism at position 801 of its 3'-untranslated region, known as SDF1-3'A. This polymorphism has been investigated in HIV-1 infection and the susceptibility to breast cancer. In this investigation 72 lung cancer patients and 262 cases of normal healthy control were investigated for the genotype frequency of SDF-1 gene. Genotype frequency was carried out by PCR-RFLP method. Of 72 cancer patients 9 (12.5%) cases were emerged with AA genotype, 38 (52.8%) patients with AG and 25 (34.7%) with GG genotype. Comparison of these data with genotype frequency of SDF-1 gene of 262 normal healthy controls indicates a significant difference among patient and control groups (P=0.008). Results also showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. By considering the importance of SDF-1 in several physiological processes and also its significant biological behavior in cancer metastasis and on the basis of the results of this study we conclude that AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian patients to lung cancer.