Nitric oxide (NO) plays complicated roles in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene is responsible for most of the NO produced. For this reason, it was considered that the eNOS gene variants is associated with cancer suspectibility. The aim of this study was to determine whether eNOS variants (G894T and intron 4 VNTR a/b) affect in Chronic Lymphocytic Leukemia (CLL) risk in Turkish patients. This is a prospective single-center crosssectional study in patients with CLL. A total of 60 CLL patients and 100 healthy controls with similar age and sex were included to this study. Two eNOS gene variants (G894T and intron 4VNTR a/b) were analysed with polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP) methods. In this study, we found that the TT genotype of eNOS G894T variant was significantly associated with an increased risk in patient with CLL compared with control (OR: 0.867, CI: 0.785-0.957, p= 0.001). There was not any significant difference in the eNOS G894T allele distribution between the groups (p > 0.05). In addition, no significant difference was detected between the CLL patients and healthy controls with respect to the frequencies of genotypes and alleles in intron 4 VNTR a/b variant of eNOS. eNOS gene variants (G894T and intron 4 VNTR a/b) in CLL patients were simultaneously analyzed for the first time in present study. Our study suggest that the eNOS G894T variant may be associated with the development of CLL in the Turkish population.