Polymorphisms of the hepatitis C virus (HCV) core protein and NS3 have been described to be associated with liver cirrhosis (LC) and/or hepatocellular carcinoma in patients with chronic hepatitis C genotype 1b (HCV 1b). Here, we determine whether there is an association between LC and polymorphisms of viral core protein and NS3 in patients in Hubei province, China. A total of 42 patients with chronic HCV 1b (21 patients with LC and 21 with chronic hepatitis [CH]) were enrolled, amino acid sequence of the core protein and N-terminus of NS3 were obtained by direct sequencing and compared with the prototype strain HCV-J. No significant difference of amino acid polymorphisms was observed between isolates from LC and CH patients in the core protein. However, in the N-terminus of NS3, amino acid polymorphisms at positions A1072T (Ala 1072 chronic Thr 1072 cirrhosis), I1074V (Ile 1074 chronic Val 1074 cirrhosis), and T1098N/I (Thr 1098 chronic Asn or Ile 1098 cirrhosis) correlated significantly with LC. These findings indicate that the polymorphisms of HCV at these sites may be the risk factors for the development of LC in patients with chronic HCV 1b.