Abstract Introduction The function of natural killer (NK) cells is regulated by different antigen receptors including killer immunoglobulin-like receptors (KIR). In addition to their important role in fighting infection, natural killer cells produce cytotoxicity against some cancer cells. Studies demonstrated that NK cells have a reduced function in chronic lymphocytic leukemia (CLL). Aim The aim of this study is to investigate KIR expression of NK cells in CLL patients to check for any association between KIR genotypes and this disease. Methods KIR genotype was analyzed for 120 healthy Lebanese patients and 56 CLL patients using the KIR Genotyping SSP kit . Results Among the 56 CLL patients, the AA, AB, and BB genotypes frequencies were, respectively, 38%, 46%, and 16% with an A:B ratio of 1.55:1. As for the controls, the AA, AB, and BB genotypes frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1. KIR 2DS4 * 001 / 002 and KIR 2DS5 were found to be significantly more prevalent among CLL patients as compared to controls. Conclusion This is the first study that reports such an interesting prevalence of KIR genes in CLL necessitating further clinical and translational research pertaining to the pathophysiology of this disease.