Studies investigating the association of polymorphisms in the 5'-untranslated regions (5'UTR) and 3'-untranslated regions (3'UTR) of thymidylate synthase with gastric cancer susceptibility and sensitivity to fluoropyrimidine-based chemotherapy report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. This meta-analysis included ten studies, which included 1,730 gastric cancer cases and 1,843 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution of 5'UTR or 3'UTR between gastric cancer and noncancer patients. When stratifying for race, we found that: (1) among Asians, patients with gastric cancer had significantly higher frequency of 2R/2R of 5'UTR than did noncancer patients, and (2) among Caucasians, patients with gastric cancer had significantly lower frequency of ins6/ins6 and higher frequency of ins6/del6 of 3'UTR than did noncancer patients. No significantly different response rate or survival of gastric cancer with fluoropyrimidine-based chemotherapy were observed with genotype distribution of 5'UTR or 3'UTR among Caucasians or Asians. This meta-analysis suggests that polymorphisms in the 5'UTR and 3'UTR of thymidylate synthase may be associated with gastric cancer susceptibility, but are not correlated with sensitivity of gastric cancer to fluoropyrimidine-based chemotherapy.