To investigate the association between polymorphisms of the COL1A1 gene and liver cirrhosis. A total of 111 liver cirrhotic patients and 95 matched controls were recruited. Polymorphisms -1997T>G, -1663 ins/del T and -1363C>G of the COL1A1 gene were detected by direct sequencing. The activities of the putative promoters containing these polymorphisms were analyzed by means of the reporter gene system. No polymorphism at -1663 ins/del T was observed in any subject. Linkage disequilibrium was shown between -1997T>G and -1363C>G. The frequency of haplotype -1997T/-1363C was significantly higher in patients than that in controls. The putative promoters containing -1997T/-1363C resulted in higher reporter gene activity in LX-2. Strong transcriptional inhibition by IFN gamma was shown in both cells. The T allele at -1997 of COL1A1 is crucial to the increased transcriptional activity. COL1A1 gene polymorphism might be associated with liver fibrogenesis.