This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC.