Hepatitis B virus (HBV) infection induces immune-mediated inflammatory responses. The C-reactive protein (CRP) is an inflammatory marker that is synthesized by the liver. The aim of the present study was to investigate the effect of HBV infection on the expression of CRP and its clinical significance. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was employed to examine the expression of CRP mRNA in the human hepatocellular carcinoma (HCC) cell lines HepG2 and HepG2.2.15. A fully automatic biochemical analyzer was used to examine the serum levels of CRP in patients with chronic HBV infections and in healthy controls. The differences in the serum CRP levels between patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and HCC were compared and analyzed. Our results showed that the expression level of CRP mRNA was higher in HepG2.2.15 cells than in HepG2 cells. The CRP serum level was significantly elevated in individuals with hepatitis B infection (P<0.05). These CRP levels were significantly higher in patients with LC and HCC than in patients with CHB. This study provides new inflammation-related aspects of investigation for understanding HCC oncogenesis caused by HBV.