Matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, is responsible for the proteolytic degradation of basement membrane and extracellular matrix. MMP-1 plays a major role in the invasion of gastric cancer (GC). The role of the genetic polymorphisms in the functional regions of MMP-1 on the risk of GC remains unclear. To identify the markers that contribute to the genetic susceptibility to GC, we examined the potential association between GC and nine single-nucleotide polymorphisms (rs 1799750, rs 498186, rs 475007, rs 514921, rs 494379, rs 996999, rs 2071232, rs 1938901, and rs 2239008) of the MMP-1 gene using the MassARRAY system in this study. The participants enrolled in this study included 422 patients with GC and 428 healthy subjects as the healthy controls from a Chinese Han population. The analysis revealed a weak association between the rs 1799750 (in the promoter region) genotype distribution and GC (p=0.020). The frequency of the 2G allele was significantly higher in the patients with GC than in the healthy controls (p=0.005, odds ratio [OR]=1.324, 95% confidence interval [CI]: 1.087-1.613). Moreover, the patients with the 2G/2G genotype of rs 1799750 had a significantly increased risk of cancer invasion compared with patients with the 1G/1G+1G/2G genotype (p=0.001, OR=0.505, 95% CI: 0.331-0.771). Strong linkage disequilibrium was observed in three blocks (D'>0.9). Significantly, more C-2G haplotypes (block 3) (p=0.0005 after Bonferroni correction) were found in GC subjects. These findings point to a role for MMP-1 promoter polymorphism in GC among a Han Chinese population, and may be informative for future genetic or biological studies on GC.