Background: High mobility group box-1 (HMGB1) induces the release of proinflammatory cytokines and chemokinesas a late-acting mediator of inflammation. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer,however, little is known about the relationship between HCC and HMGB1 and its receptor RAGE (receptor for advancedglycation end products). We studied the clinicopathological relevance of the expression level of HMGB1 and the effect ofHMGB1 expression on the characteristics of HCC.Methods: Samples from the 36 HCC patients including 7 with positive hepatitis B surface antigen and 21 with hepatitisC antibody were studied. Twenty-four patients had chronic active hepatitis and 4 had liver cirrhosis. The expression ofHMGB1 was assessed in paired cancerous and noncancerous tissues with HCC, using reverse-transcription polymerasechain reaction (RT-PCR), and Western blotting. Quantitative RT-PCR data were analyzed relation to clinicopathologicalfeatures. As a control study, 7 normal liver samples were collected from patients other than HCC. Results: The expression of HMGB1 mRNA was lower in normal liver than in noncancerous tissue and the highestin HCC, although the differences were not significant. Furthermore, in HCC, it was high in well- and moderatelydifferentiated tumors but declined as tumors dedifferentiated to poorly differentiated HCC (p=0.033). The expressionlevel was inversely correlated with tumor recurrence (p=0.036). No significant correlations were observed between theexpression levels and well-known prognostic factors of HCC (e.g. portal invasion and intrahepatic metastasis).Conclusion: In HCC, HMGB1 expression level correlated inversely with the patient’s prognosis. The HMGB1 mRNAexpression level is similar to the level we reported previously in a study on the clinicopathological relevance of the level ofRAGE in HCC. RAGE-HMGB1 interaction in HCC might work in the early stage of tumorigenesis more than in the stage ofcancer development.