Accumulating evidence has identified that polymorphism residing in the microRNA (miRNA) binding site of target genes can affect the strength of miRNA binding and influence individual susceptibility to cancer. Recently, an insertion/deletion polymorphism (rs3783553 ttca/-) at miRNA-122 binding site in the interleukin-1A 3' untranslated region has been demonstrated to be functional. We aimed to investigate the association between the rs3783553 polymorphism and the risk of gastric cancer (GC). We genotyped the rs3783553 polymorphism in 207 GC patients and 381 healthy controls by using a polymerase chain reaction method. We found that the ins/ins (ttca/ttca) genotype of the rs3783553 polymorphism was associated with a significantly decreased risk of GC (P = 0.02, odds ratio = 0.48, 95% confidence interval 0.26-0.90). This finding suggests that the rs3783553 polymorphism may be a protective factor for the development of GC.