Abstract. The aim of the present study was to evaluate and compare the treatment efficacy and cost of two therapies, splenectomy and thrombopoietin, in order to optimize the treatment plans for patients with HCV-associated cirrhosis. A prospective randomized controlled trial was conducted on 69 patients with a platelet count <60,000/mm 3 that were enrolled between 2009 and 2013, including 38 cases as the research group and 31 cases as the observed group. The study included two stages: A 4-week initial treatment and a 48-week antiviral treatment, during which a number of parameters were evaluated, including platelet count, liver stiffness measure, albumin, total bilirubin, alanine aminotranferase and treatment cost-effectiveness. Of the 38 patients, 21 underwent a splenectomy and their platelet counts increased to 60,000/mm 3 after the 4-week initial treatment. The patients then started a 48-week P-R antiviral treatment, and 18 cases completed the treatment. In addition, 17/38 patients received thrombopoietin as a drug therapy. The platelet counts in 15 cases increased to >60,000/mm 3 and the patients received antiviral treatment, among which 9 cases completed the second treatment stage. The expense of the splenectomy group treatment was higher compared with that received by the thrombopoietin group. The results of the present study indicated that splenectomy was more effective at increasing platelet count. More splenectomy patients completed the full course of antiviral treatment and presented a sustained virologic response, compared with the thrombopoietin group. Therefore, splenectomy may be more expensive compared with thrombopoietin; however, the improved efficacy suggests that on balance it is the preferable treatment option.