Research studies have concluded that the poor prognosis of HCC is associated with several clinicopathological parameters, such as poorly differentiated phenotype, portal venous invasion and intrahepatic metastasis. However, the underlying mechanisms associated the development of HCC have not been understood completely. HMGB1 was originally described as a nuclear non-histone DNAbinding protein that functions as a structural co-factor critical for proper transcriptional regulation in Regorafenib msds somatic cells. HMGB1 is highly conserved through evolution, and although it is produced by nearly all cell types, its nuclear localization can vary with development and age. Structurally, HMGB1 has 215 residues organized into two DNA-binding domains, and a negative charged C-terminus. The two DNAbinding domains are similar in conformation despite to their limited amino acid identity. HMGB1 is a versatile protein with intranuclear and extracellular functions. HMGB1 is a highly conserved nuclear protein, because itacts as a chromatin-binding factor that bends DNA. HMGB1 alsoinstigates access to transcriptional protein assemblies located on specific DNA targets. HMGB1 acts as an extracellular signaling molecule during several cellular processes, such as inflammation, cell differentiation, cell migration, and tumor metastasis. Previous research studies have confirmed that HMGB1 is closely related with tumorigenesis, metastasis, and angiogenesis in a variety of malignancies, such as breast cancer, melanoma, gastric cancer, and colorectal cancer.An overexpression of HMGB1 occurs due to two main reasons: KIT mutation and genes instigating tumour growth and invasion. Furthermore, HMGB1 overexpression has been associated with several undesirable activities: inhibition ofcaspase activation, increase in NF-kB activity, and up-regulation of c-IAP2.Thus, the overexpression of HMGB1 inhibits the apoptosis of cancer cells. In this study, we investigated the expression of HMGB1 in primary HCC using immunohistochemical analysis. We also identifiedhow HCC was related with different kinds of clinicopathological features.Furthermore, we evaluatedthe prognostic significance of HMGB1expression in the survival of HCC patients. There have been major breakthroughs in the diagnosis and chemotherapy measures used in the treatment of cancer. However, HCC continues to be one of the most deadly human carcinomas, and the prognosis of HCC remains dismal.In clinical practice, prognostic molecular biomarkers are valuable toolsin predicting the progression of disease in patients. And these patients we selected are at early or intermediate stage of hepatocellular carcinoma patients in our study. Clinicians use these prognostic biomarkers in planning strategies that control the proliferation of tumor. In this study, we determined the HMGB1 expression in HCC patients. We also explored the clinical prognostic significance of HMGB1 expression.