To study the expression of interferon-alpha/beta (IFN-alpha/beta) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance.A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-?1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-alpha/beta receptor (IFN-alpha/betaR) protein in liver of all patients was determined with immunofluorescence.In liver of patients with HCV-related chronic liver disease, the expression of IFN-alpha/betaR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-alpha/betaR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-alpha/betaR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group.Expression of IFN-alpha/betaR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.