Objective: We planned this study to investigate the relation between serum adiponectin level and hepatocel-lular carcinoma (HCC): risk, features and prognosis. Methods: The study included 100 patients with HCC and 40 healthy control subjects. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. Results: In the subset of patients with compensated cirrhosis, the mean serum adiponectin level was significantly lower in HCC cases compared to healthy controls (88.6 versus 115 ng/mL; P = 0.012). In addition, serum adiponectin levels correlated negatively with tumor size (P = 0.004) and were significantly lower in patients with vascular invasion and distant metastases (P = 0.03 and P = 0.02 respectively). Furthermore, the median overall survival was significantly higher in the high adiponectin group than the low adiponectin group (median 12.5 versus 9.5 months; log rank = 4.6, P = 0.03). Conclusion: Decreased circulating adiponectin level may play a role in the development of HCC and is a potential poor prognostic marker. These data should be validated in further prospective studies. Also the mechanisms by which adiponectin affect the course of HCC need to be clarified.