The reasons for the viral persistence of hepatitis B virus (HBV) infection are unknown, but are probably related to host immune factors. Several matrix metalloproteinases (MMPs) can regulate an inflammatory response. The aim of this study was to assess the effects of the single nucleotide polymorphisms (SNPs) of MMP-3 and -9 genes on the susceptibility to persistent HBV infection. We studied 489 Korean patients with HBV infection (144 inactive carriers, 182 chronic hepatitis, and 163 liver cirrhosis) and 174 healthy individuals who had recovered from HBV infection. MMP-3 gene SNPs were identified at two polymorphic sites (codon 45 [E45K] and codon 96 [D96D]) and MMP-9 gene SNPs at three polymorphic sites (codon 279 [R279Q], codon 607 [G607G], and codon 668 [Q668R]) in study subjects. The frequency of T allele at third position of codon 96 in the MMP-3 gene was higher in HBV persistence patients when analyzed by co-dominant model (age- and sex-adjusted OR=1.242, 95% CI=1.001-1.540, p=0.049). In conclusion the T allele at the third position of codon 96 in the MMP-3 gene might be associated with persistent HBV infection.