Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functionalpolymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associationsbetween MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understandthe role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensivemeta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism wasassociated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI =1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, thispolymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02-1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA,OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophagealSCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI= 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-basedstudies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to thesource of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model(GG vs. AA, OR=1.40, 95% CI=1.12–1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02–1.51), anddominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08–1.55). Our findings suggest that the MMP-7 (-181A>G)polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.