Matrix metalloproteinase-13 (MMP-13) belongs to a family of enzymes that degrade all components of the extracellular matrix. Polymorphism in the promoter region of the MMP-13 gene may modify its transcriptional activity and protein level. This study was designed to investigate the correlation of MMP-13 A-77G single nucleotide polymorphism (SNP) with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac carcinoma (GCA) in a population from a high-incidence region of Hebei province. MMP-13 promoter SNP (A-77G) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 316 ESCC patients, 243 GCA patients and 609 healthy controls. The overall genotype and allelotype distributions of MMP-13 in ESCC and GCA patients were not significantly different from those in healthy controls (P>0.05). When stratified for smoking status, the A/A, A/G, G/G genotype frequencies of MMP-13 in GCA patients and smoker controls group were 27.1%, 44.1%, 28.8% and 17.8%, 60.5%, 21.7% respectively. There was a significant difference between the two groups (chi2=9.01, P=0.01). The A/G genotype frequency in GCA patients was significantly lower than that in the controls, when compared to the A/A genotype, suggesting that individuals with the A/G genotype may have reduced susceptibility to GCA in the smoker group (OR=0.48, 95% CI=0.280.83). However, the G/G genotype showed no significant influence on the risk of developing GCA. Thus, in the region of Hebei Province where there is a high incidence of GCA and ESCC, the MMP-13 A-77G SNP may not be associated with cancer susceptibility. The A/G genotype may confer protection against GCA for smokers.