Aim: Serum alpha-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC. Method: A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects (n = 29), chronic hepatitis B or C (n = 50), non-HCC tumors (n = 23) and HCC (n = 26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects. Results: The expression of IL-6 or IL-10 (>= 3 pg/ml), or high level of HGF (> 1000 pg/ml) or AFP (> 20 ng/ml) was observed in only 0-3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels (p < 0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (< 20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC (p < 0.05). Patients with large (> 5 cm) HCC more often had increased IL-6, IL-10 or AFP levels (p values all < 0.05). Conclusions: Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients. (c) 2006 Elsevier Ltd. All rights reserved.