Purpose: Over the past three decades, Hepatocellular Carcinoma (HCC) is one of few cancers for which incidence has increased in the United States (US). It is likely social determinants at the population level are driving this increase. We designed a population-based study to explore whether social determinants at the neighborhood level are geographically associated with HCC incidence in Louisiana by examining the association of HCC incidence with neighborhood concentrated disadvantage.Methods: Primary HCC cases diagnosed from 2008 to 2012 identified from the Louisiana Tumor Registry were geocoded to census tract of residence at the time of diagnosis. Neighborhood concentrated disadvantage index (CDI) for each census tract was calculated according to the PhenX Toolkit data protocol based on population and socioeconomic measures from the US Census. The incidence of HCC was modeled using multilevel binomial regression with individuals nested within neighborhoods.Results: The study included 1,418 HCC cases. Incidence of HCC was greater among males than females and among black than white. In multilevel models controlling for age, race, and sex, neighborhood CDI was positively associated with the incidence of HCC. A one standard deviation increase in CDI was associated with a 22% increase in HCC risk [Risk Ratio (RR) = 1.22; 95% CI (1.15, 1.31)]. Adjusting for contextual effects of an individual's neighborhood reduced the disparity in HCC incidence.Conclusion: Neighborhood concentrated disadvantage, a robust measure of an adverse social environment, was found to be a geographically associated with HCC incidence. Differential exposure to neighborhoods characterized by concentrated disadvantage partially explained the racial disparity in HCC for Louisiana. Our results suggest that increasing rates of HCC, and existing racial disparities for the disease, are partially explained by measures of an adverse social environment.