We examined the association of TIMP-1 and TIMP-2 gene polymorphisms with the progression of chronic liver disease related to the hepatitis C virus (HCV). We used PCR to analyze 188 patients with HCV-related liver disease (95 with chronic hepatitis and 93 with cirrhosis) for TIMP-1 372 T/C and TIMP-2 -418 G/C polymorphisms. Comparing chronic hepatitis and cirrhosis, there were no significant differences in TIMP-1 and TIMP-2 gene polymorphisms. Among chronic hepatitis patients, TIMP-2 -418 G homozygotes showed significantly faster fibrosis progression than C carriers. Among cirrhotic patients, males with the TIMP-1 372 T allele developed cirrhosis at a younger age, and patients who were homozygous for the higher-transcription TIMP-2 -418 G allele had significantly lower serum albumin concentrations. These results suggest that faster progression of liver fibrosis could be associated with TIMP-2 -418 G homozygotes.