The objective of this study was to explore the association between statins use and risk of developing hepatocellular carcinoma (HCC). We used the research database of the Taiwan National Health Insurance program to conduct a population-based case-control study. Cases were 3,480 patients with newly diagnosed HCC identified during 2000 and 2009. Controls were 13,920 subjects without HCC and frequency matched for age, sex and duration of observational period of cases (i.e., the duration between year of being enrolled in the insurance program and index year of cases). Six commercially available statins, including simvastatin, lovastatin, fluvastatin, atorvastatin, pravastatin, and rosuvastatin, were analyzed. The adjusted odds ratio [OR] of HCC was 0.72 [95% (CI) 0.59-0.88] for the group with stains use, when compared to the group with non-use of statins. In sub-analysis, simvastatin (OR 0.69, 95% CI 0.50-0.94), lovastatin (OR 0.52, 95% CI 0.36-0.76) and atorvastatin (OR 0.70, 95% CI 0.53-0.93) were associated with significant reduction in odds of HCC. Statins use correlates with 28% decreased risk of HCC. Individual statins, including simvastatin, lovastatin and atorvastatin, are associated with reduced risk of HCC.