There is a marked variation in the outcome of patients with hepatocellular carcinoma with respect to race and ethnicity. Rates among African American and Hispanic individuals are elevated as compared with those among white individuals. Retrospective review of a prospective database. Demographic information, clinical staging, and other defining factors, including the absence or presence of hepatitis, cirrhosis, and alcohol abuse, were analyzed by patient interviews and review of the medical record. Urban tertiary referral teaching hospital. Patients diagnosed as having hepatocellular carcinoma between July 1997 and June 2003 (N = 264). Main Outcome Measure Overall survival rates. Based on multivariate analysis, race was identified as an independent predictor of survival. While there was no difference in the distribution of patient or tumor characteristics between the 2 groups, African American/Hispanic patients had a 5-year survival rate of 12%, which was significantly lower than that of white patients (50%; P = .001). This study demonstrates a significant discrepancy in overall survival of African American/Hispanic patients as compared with that of white patients. The reason for this difference cannot be explained by patient or tumor characteristics or completely by treatment allocation. These data suggest that there may be socioeconomic, biological, and/or cultural determinants contributing to this observed difference in outcome.