Background: Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study,we investigate the effect of alcohol consumption and folate intake onHCCincidence and liver disease mortality in the NIH-American Association of Retired Persons Diet and Health Study. Methods: The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. Results: Consumption of more than three drinks per day was positively associated with bothHCCincidence (HR: 1.92; 95%CI: 1.42-2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81-7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction 0.54). Conclusions: These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. Impact: Folate intake may be beneficial in the prevention of alcohol-associated HCC.