Thrombocytopenia is a common finding in patients with chronic liver disease related to hepatitis C virus (HCV) infection. Interferon therapy may aggravate thrombopenia through the inhibition of platelet production, leading to premature discontinuation of therapy, dose reduction, and viral relapse. The use of thrombopoietin agonists (romiplostim and eltrombopag) seem to be a useful way to increase the platelet count and facilitate interferon therapy in patients with a chronic HCV infection. Here, we report on the first two cases of patients with HCV-related cirrhosis successfully treated for HCV infection following an increase in the platelet count with romiplostim. Severe thrombocytopenia developed in both patients at weeks 22 and 12 of antiviral therapy, respectively. Considering the risk of relapse in the case of interferon dose reduction or early treatment discontinuation, we initiated platelet growth factor therapy with romiplostim. This approach allowed us to maintain a reasonable platelet count (>50 × 10⁹/l) and completion of an anti-HCV protocol without dose reduction, achieving a sustained virological response.