Background: Liver cancer is the most frequent cancer among Thais especially people in northeastern Thailand, but there has as yet been no assessment of trend. The data of all cancers in Khon Kaen can be retrieved from data base of the Khon Kaen Cancer Registry (KKCR) which was established in 1984. Objective: To assess the incidence trend of hepatocellular carcinoma in Khon Kaen, Thailand, between 1990 and 2009. Methods: Population-based cases of liver cancer registered between 1985 and 2009 were retrieved from the KKCR data base and cases with diagnosis of hepatocellular carcinoma (HCC) with the coding C22.0 according to ICD-O were selected. Incidence trends were calculated using the Jointpoint analysis. Results: There were 7,859 cases of HCC during the study period. Males were affected two times more frequently than females. The most common age group of cases was 50 and 69 years (60.3%). Most patients were diagnosed based on radiology imaging (40.6%) while the morphology verification was 7%. The age-standardized rates (ASR) were 13.1 to 49.8 per 100,000 among males and 4.8 to 38.4 per 100,000 among females depending on year of diagnosis since 1985. Remarkably, the ASRs were clearly low during first few years of starting the registration. The overall ASRs of HCC were 30.3 per 100,000 in males (95% CI: 25.9 to 34.6) and 13.1 per 100,000 (95% CI: 10.4 to 15.8) in females. During 1990-2009, the trends in incidences have been decreasing significantly with the annual percent change (APC) of 6.2% per year (95% CI: -7.6 to -4.8) in males and by 6.5% per year in females (95% CI: -8.4 to -4.9). Conclusions: The incidence trends have been decreasing in both sexes. The recent decline in incidence may represent a falling risk.