Background: Diffuse large B-cell lymphoma (DLBCL) has heterogeneity in its behavior, and pathological and molecular identification. Hematopoiesis is regulated by microRNAs thus its aberrant expression predisposes to myeloid and lymphoid neoplasms the current research aimed to explore serum miR- 26a-5p and miR-199b-5p in patients with DLBCL and to evaluate its correlation with clinicopathological features and treatment protocols of NHLs among Egyptian patients with Hepatitis C virus (HCV)Infection. Methods: We enrolled 60 participants; 30 patients with DLBCL and 30 healthy persons as the control group. all subjects were screened for the presence of HCV-RNA in both plasma and PBMCs. miR-26a-5p and miR- 199b-5p levels were determined by RT-PCR.Results: Serum miR-26a-5p and miR-199b-5p level values were downregulated in DLBCL patients with HCV and OCI compared to non-HCV and controls. There were significantly higher values of both miR-26a-5p and miR-199b-5p levels in patients with complete response(n=15,50%) compared to partial response (n= 5,16.7%) and primary refractory (n=10,33.3%), p˂0.001. Noteworthy, there were statistically significant negative correlations between miR-26a-5p, miR- 199b-5p, LDH, and total bilirubin. Linear regression tests revealed that among examined associated variables, only LDH was the independent variable associated with miR-26a-5p and miR-199b-5p, P ˂0.001. Conclusions:Serum miR-26a-5p and miR-199b-5p levels were down regulated in DLBCL patients, especially with HCV infection. Thus, these epigenetic markers could provide a new era of precision medicine to better refine diagnosis, prognostication, and rational treatment Keywords: miR- 26a-5p; miR-199b-5p; Diffuse large B-cell lymphoma; Occult hepatitis C; RCHOP.