Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single‐nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA‐mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa‐mir‐27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR‐27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case‐control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06–2.05; P = 0.019). The elevated risk was especially evident in older subjects (age >58 years), men, nonsmokers and rural subjects. A significant association of hsa‐mir‐27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR‐27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR‐27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa‐mir‐27a, by modulating miR‐27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility. (Cancer Sci 2010)