In chronic liver disease associated with hepatitis C virus (HCV), a low platelet count is a major obstacle in carrying out interferon (IFN) treatment. We used a questionnaire to clarify the extent to which splenectomy/partial splenic embolization (PSE) is performed before IFN treatment, as well as the efficacy and complications thereof. Two questionnaires were distributed to 413 medical institutes in Japan specializing in the treatment of liver diseases, and responses were obtained from 204 institutes. Furthermore, a more detailed questionnaire was completed by 10 institutes that experienced cases of death. In patients with HCV genotype 1b and a high viral load (HCV1b/High), the sustained viral response (SVR) rate was 28% for the splenectomy group and 22% for the PSE group, with no significant difference between these groups. In patients that were not HCV1b/High, the SVR rate was higher in those that underwent splenectomy (71%) compared to the PSE group (56%; P = 0.025). There were cases of death in seven of 799 splenectomy cases (0.89%) and four of 474 PSE cases (0.84%). Infectious diseases were involved in nine of 11 cases of death, with a peculiar patient background of Child-Pugh B (6/10) and an age of 60 years or greater (7/11). The application of splenectomy/PSE before IFN treatment should be avoided in patients with poor residual hepatic function and/or elderly patients. In HCV1b/High patients, splenectomy/PSE should be performed only after selecting those in which IFN treatment should be highly effective.