Background: Hepatocellular carcinoma (HCC) is a common trouble all over the world, with highest mortality rate in both males and females. Hepatocarcinogenesis caused by Hepatitis C virus (HCV) results from alterations that may be caused from viral causes or immune mediated as a consequence of chronic inflammation. MicroRNAs (miRNAs) are collections of noncoding RNA contain around 18–25 nucleotides long to influence post-translational gene expression, have been revealed to become involved in HCC outcome. Objective: To determine the association of pri-miR-34b/c rs4938723 (T>C) and miR-146a rs2910164 (C>G) polymorphisms of the Egyptian patients with the risk of the development of HCC which might serve as biomarkers for early diagnosis/prognosis of HCC. Patients and Methods: Thirty five HCC patients, thirty five HCV infected patients, and thirty age and gender matched healthy controls included in this work. Pri-miR-34b/c rs4938723 (T>C) and miR-146a rs2910164 (C>G) polymorphisms were assayed with real time-PCR genotyping assays. This study was carried out over a period from January 2019 and April 2020, at Theodor Bilharz research institute (TBRI). Results: A significant increase in miR-34b/c TT genotype within HCC group and HCV group in comparison to control group was observed (p value = 0.01 and 0.001 respectively). In addition, there was a significant increase in pri-miR-34b/c T alleles in HCC group (p value = 0.03) and HCV group (p value = 0.01) compared to control group. Conclusion: Pri-miR-34b/c TT genotype might serve as a risk factor for HCC development in HCV infected Egyptian population.