Aims: the current study aimed to investigate the role of miR-150-5 p expression as a diagnostic and prognostic marker of B- CLL among Egyptian patients with chronic hepatitis C and its impact on risk stratification and response to therapy. Patients & Methods: This study was conducted on 25 patients with chronic hepatitis C recently diagnosed as CLL and 25 healthy control All studied patients were subjected to entire history, taking the complete clinical examination, and laboratory investigations including serum LDH, serum β2 microglobulin (β2M), CD38 and ZAP70 expression by flow cytometry. We measured miR-150-5 p expression by qRT-PCR. Results: The results of this analysis indicated that CLL patients had a significantly lower level of miR-150-5 p expression (0.464±0.16) compared to the control group (0.8±0.76), P ˂0.001* Additionally, the expression levels of miR-150-5 p were significantly inversely correlated with laboratory and clinicopathological features of CLL as well as the severity of CLL according to Modified Rai staging system and Binet staging system. Interestingly, concerning the treatment of CLL, there were significantly lower levels of miR-150-5 p in no treatment subgroup (n=18, 0.49±0.13) compared to successfully treated subgroups (n=7, 0.77±0.07), P ˂0.001* Conclusions: miR-150-5 p expression level was downregulated in CLL patients, particularly patients with HCV infection, and significantly inversely correlated with the severity of CLL. Thus, it could be helpful for diagnostic and prognostic purposes in CLL.