BACKGROUND:Hepatocellular carcinoma (HCC) is the fifth leading cause of death in Japan. The aim of this study was to calculate the social burden of HCC using the cost of illness (COI) method, and to identify the key factors driving changes in the economic burden of HCC. METHODS:Utilizing government-based statistical nationwide data, the cost of illness (COI) method was used to estimate the COI for 1996, 1999, 2002, 2005, 2008, and 2014 to make predictions for 2017, 2020, 2023, 2026, and 2029. The COI comprised direct and indirect costs (morbidity and mortality costs) of HCC. RESULTS:From 1996 to 2014, COI trended downward. In 2014, COI (579.2 billion JPY) was 0.71 times greater than that in 1996 (816.2 billion JPY). Mortality costs accounted for more than 70% of total COI and were a major contributing factor to the decrease in COI. It was predicted that COI would continue a downward trend until 2029, and that the rate of decline would be similar. CONCLUSIONS:COI of HCC has been decreasing since 1996. Treatment of patients infected with hepatitis C virus using newly introduced technologies has high therapeutic effectiveness, and will affect the future prevalence of HCC. These policies and technologies may accelerate the downward tendency of COI, and the relative economic burden of HCC is likely to continue to decrease.