Liver cirrhosis is the main risk factor for the development of human hepatocellular carcinoma (HCC). In this condition, the liver and plasma suffer a drastic depletion of retinoids. This study was conducted to investigate whether any relation exists between serum retinol levels and HCC development in cirrhotics. Seventy child-Pugh class A cirrhotic patients, 16 child-Pugh class A cirrhotic patients with HCC, and 140 age- and sex-matched subjects were included in this study. At the time of enrollment, fasting blood samples were taken to determine serum retinol levels. For the following 7 years, the 70 cirrhotic patients were also followed up for the occurrence of HCC by periodic screening with ultrasonography and serum alpha-fetoprotein assays. The serum retinol levels in both cirrhotic patients and HCC patients were significantly lower than those in healthy subjects. Among the 70 cirrhotic patients, 14 HCC were detected during follow-up. The prediagnostic retinol levels were significantly lower in cirrhotic patients who developed HCC compared with patients who did not. The odds ratio of cirrhotic patients who developed HCC in the lowest tertile to highest tertile of retinol status was 6.75 (95% CI=1.26--36.0; P=0.015). Our results suggest that a state of retinoid deficiency may promote hepatocarcinogenesis in patients at high risk such as cirrhotics.