OBJECTIVES There exists a lack of studies for cost-effectiveness analysis on treating hepatocellular carcinoma (HCC). This study aimed at estimating life expectancy (LE), lifetime costs, and incremental cost-effective ratios (ICER) for five different treatments of HCC, using a semiparametric method. METHODS A retrospective cohort study was performed of a 1,000,000-person random sample obtained from Taiwan's National Health Insurance (NHI) reimbursement database. A total of 1932 newly-diagnosed patients with HCC were indentified and verified with independent file of catastrophic illnesses. These patients were followed from 1997 to 2003 with longitudinal claim data, including all orders and costs of inpatient services, outpatient services, and prescriptions dispensed at pharmacies. They were further stratified to five subgroups with different treatments, comprised of surgery, percutaneous ethanol injection (PEI), transarterial chemoembolization (TACE), chemotherapy and radiotherapy, and supportive care. The lifetime survival (up to 50 years) was estimated using the Monte Carlo method as well as borrowing information from the general population. The lifetime costs were estimated by integrating the lifetime survival function and cost function with some assumptions after the follow-up limit. The ICER was also calculated as the net cost of four different treatments study groups divided by the increased number of life years, compared with the supportive care. RESULTS The LE on overall HCC patient was 35.73 months. The surgery group had the longest LE (85.73 months), and the supportive care group had the shortest LE (15.97 months). The surgery was the most cost-effectiveness treatment, which the ICER was 2358 USD per life year (LY) after lifetime follow-up. The PEI (7124 USD/LY) was more cost-effective than TACE (7767 USD/LY). CONCLUSIONS The study applied semiparametric method to project lifetime survival and lifetime costs, using the real cost data through national longitudinal reimbursement database, which might be an alternative method with retrospective approach on cost-effectiveness analysis.