Objective: The American Association for the Study of Liver Diseases 2005 practice guidelines recommended that various groups at different levels of risk to hepatocellular carcinoma (HCC) undergo surveillance. This study aimed to assess which high risk group had the lowest incremental cost-effectiveness ratio (ICER) for the HCC screening program from the insurer's perspective. Methods: The high risk subjects were identified from the communities with high prevalence of hepatitis viral infection and classified into three groups at different levels of risk to HCC at the time of enrollment. The repeated ultrasound screenings at an interval of three, six, and twelve months were applied to cirrhosis group, early cirrhosis group, and no cirrhosis group, respectively. The Markov-based decision model was constructed to simulate progression of HCC and to estimate the ICER for each group over a time horizon of 50 years or the subjects' remaining life expectancy. Validity of the model outcomes was examined against the health statistics. Results: The incremental ICER for the cirrhosis group, early cirrhosis group, and no cirrhosis group were $1375, $816, and $861, respectively. Among the three groups, the early cirrhosis group had the highest incremental effect (3.41 years per person) and the cirrhosis group had the largest incremental cost ($4247 per person). It is noteworthy that when compared to the other two groups, the cirrhosis group showed the lowest incremental effect (2.03 year) and the highest incremental cost ($4247). Conclusion: Screening the no cirrhosis group for HCC at a 12-month interval had the lowest incremental cost-effectiveness ratio.