Background: Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in adults presenting with varied clinical course. There is a higher request for founding known prognostic factors for stratifying CLL patients. HLA-G is a non-classical major histocompatibility complex (MHC) molecule. It can be expressed in membrane bound (m.HLA-G) and soluble forms (s.HLA-G). Objective: The aim of work was to investigate the expression of membrane form of HLA-G in CLL and correlate findings and a variety of clinical and laboratory variables. Patients and methods: This prospective study included a total of thirty newly diagnosed B-CLL patients, attending at Hematology Unit, Medical Oncology Department, national Cancer institute, Cairo. This study was conducted between December 2017 to July 2019. Diagnosis of CLL was confirmed by flow cytometric immunophenenotyping using standard lymphoma panel, membrane HLA-G was determined by flow cytometry. Results: The expression of HLA-G by flowcytometry was negatively correlated with the platelet count (r = -0.516, p = 0.004) and Hb (r = -0.479, p = 0.007). The expression of HLA-G was significantly higher in CD38 positive cells (p = 0.006). The expression of HLA-G was significantly higher in Rai stage 4 compared to stage 1 & stage 2 (p = 0.001). Conclusion: It could be concluded that expression of HLA-G might represent signs of immunosuppression in CLL patients which contribute to the immune escape of tumor cells. In addition, HLA-G expression by B-CLL cells correlates significantly with the known prognostic markers of disease progression, mainly Rai clinical staging, CD38 expression and worse survival, making this parameter possibly an important prognostic factors of disease progression.