Aims: To assess if the rising incidence of hepatocellular carcinoma in the United States can be accounted for by immigration and an ageing population, or is a true increase among the USA-born residents. Methods: Design - A retrospective chart review. Setting - Urban, multiethnic hospital and specialty clinics in a large indigent health system in Houston, Texas. Subjects - Approximately 23 000 admissions and 143 000 out-patient clinic visits each year from 1992 through 2001 were assessed. A total of 494 patient records were selected and reviewed because of suspicion of hepatocellular carcinoma. Analysis - Hepatocellular carcinoma was confirmed by histopathology, α-fetoprotein level >400 ng/mL, and suggestive imaging studies. The age-adjusted, incidence was determined and causative factors were identified. Results: About 111 cases of confirmed hepatocellular carcinoma were found. The age-adjusted incidence rose from 3.44 per 100 000 hospital admissions during 1992-1996 (95% confidence interval: 2.86-4.02) to 5.19 during 1997-2001 (95% confidence interval: 4.41-5.97). The proportion of patients of non-USA place of birth decreased between 1992-1996 and 1997-2001 (46-24%, respectively, P = 0.03). Fifty-two per cent and 68% were hepatitis C virus-positive respectively; 37% and 34% were hepatitis B surface antigen-positive respectively; 46% and 59% had a history of alcohol abuse; and 22% and 11% had no identifiable risk factors. Conclusions: The incidence of hepatocellular carcinoma within the greater Houston area has increased during the past decade, rising by 51% from 1992-1996 to 1997-2001. This increase is not from immigration or population ageing but represents a true rise among the native born population. Hepatitis C and alcoholic cirrhosis are associated with a majority of cases, particularly in the latter half of the decade.