In present study, we demonstrated that the expression of HMGB1 was significantly higher in HCC tissue, compared to that in para-tumor and normal liver tissue, high expression of HMGB1 was significantly associated with incomplete tumor encapsulation and advanced TNM stage, and for the first time, we revealed that high expression of HMGB1 predicted poorer survival for patients with HCC after curative hepatectomy, especially for patients with tumor >5 cm. This evidence concerns the gene HMGB1 and hepatocellular carcinoma.