C-reactive protein (CRP) is known to be associated with poor prognosis in patients with various malignancies. We investigated the relationship between the pretreatment serum CRP level and survival in patients with hepatocellular carcinoma (HCC) in various stages of the disease. A cohort of 133 patients with newly diagnosed HCC was prospectively evaluated. The patients were divided into two groups: high-CRP group (n=27) with the pretreatment serum CRP level≧1.0 mg/dl and low-CRP group (n=106) with the CRP level<1.0 mg/dl. They were followed 22 months in average (1-69 months) and clinicopathological variables, and overall survivals between the two groups were compared at the end of the follow-up period. There was a significant difference between the two groups in aspartate aminotransferase, alanine aminotransferase, total serum bilirubin, albumin, α-fetoprotein level, maximal tumor diameter, frequency of vascular invasion and extrahepatic metastases. Patients in the high-CRP group had higher Child-Pugh scores, higher Cancer of the Liver Italian Program scores and higher Japan Integrated Staging scores than patients in the low-CRP group. The overall survival rates in the high-CRP group were significantly lower than those in the low-CRP group. Survival rates were similar in tumor stage and liver function-matched patients. On multivariate analysis, pretreatment serum CRP level was independently associated with overall survival. Our results demonstrate that the pretreatment serum CRP level is associated with tumor progression and reduced liver function and is an independent poor prognostic marker in patients with HCC.