In post-genomic era, it is hypothesized that abnormal expression of matrix metalloproteinase 8 (MMP8), an collagenase in charge of regulating the extracellular matrix, may play a critical role in the development of gastric cancer, which is one of the global leading causes of death. Since the importance’s of MMP8 genotype/phenotype has never been studied in literature about gastric cancer in Taiwan and all over the world, our aim is to investigate MMP8 promoter (C-799T) and exonic (Lys460Thr and Val436Ala) genotypes and gastric cancer susceptibility in a central Taiwan population based on China Medical University and Hospital. In the current study, the association of MMP8 C-799T, Lys460Thr and Val436Ala genotypes with gastric cancer risk was examined and evaluated among 121 gastric cancer cases and 363 gender- and age-matched non-cancer subjects via the typical genotyping methodology, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). In the results, we have noticed a slight but not-significant difference in the distribution of T allelic frequencies of the MMP8 C-799T genotype (odds ratio [OR]=0.86, 95% confidence interval [CI]=0.62-1.19, P=0.3669), but not in those exonic polymorphic sites, between the gastric cancer case and control groups. Those who had CT or TT variant genotypes at MMP8 C-799T showed a 0.89-and 0.73-fold (95%CI=0.57-1.38 and 0.35-1.56, P=0.6027 and 0.4189, P for trend =0.6813) risk of gastric cancer compared to those with CC. The risk CT and TT genotypes at MMP8 C-799T, Lys460Thr or Val436Ala have no synergistic effect with alcohol drinking, cigarrete smoking nor Helicobacter pylori infection status on gastric cancer risk determination. Overall, the pilot study suggested that the three polymorphic sites of MMP8 may contribute to gastric carcinogenesis non-significantly and may not be a practical biomarker for gastric cancer early detection and prevention, at least in Taiwan population.