The role of microRNA 155 (miRNA 155) and the immunological checkpoint cytotoxic T-lymphocyte associated antigen 4 ‎‎(CTLA-4) in chronic liver diseases and hepatocellular carcinoma (HCC) are complex. The alterations in the expression levels or ‎functions of CTLA-4 and miRNA 155 could influence the outcome of HCV infection by affecting the quality and persistence of ‎the antiviral immune response. Here, we tried to investigate the relationships of miRNA 155 gene expression with CTLA-4, the ‎regulator gene of lymphocyte activation in patients with HCC and chronic HCV infection to assess the interactions between these ‎genes and lymphocyte activation and its contribution in liver disease progression. A case-control study included 80 subjects (20 ‎healthy controls, 20 HCV patients without cirrhosis, 20 with liver cirrhosis, and 20 patients with HCC). The expression of ‎miRNA 155 and CTLA-4 gene were measured by quantitative real-time qRT-PCR. The percentage of circulating regulatory T (T ‎reg) cells expressing CD4 and CD25 was done by flow cytometry. Results revealed that miRNA 155 and CTLA-4 gene were ‎upregulated with higher expression in HCC and liver cirrhosis patients compared to HCV without liver cirrhosis and control ‎groups (p value < 0.05). Together with a significant increase in CD4+CD25+ T reg in HCC and liver cirrhosis patients ‎compared to the HCV group (p value <0.05). In conclusion, miRNA 155 and CTLA-4 gene could be utilized as new ‎biomarkers in HCV- induced liver fibrosis and HCC for further exploration of immunomodulatory strategies targeting these ‎molecules to enhance antiviral immune responses and prevent hepatocarcinogenesis.‎