MicroRNAs (miRNAs) are small non-coding RNAs that inhibit the expression of target protein-coding genes, most often at the post-transcriptional level. miRNAs are often found to be misregulated in human cancer and they can act as potent oncogenes or tumor suppressor genes. In this study, we found that a germline mutation in the miR-125a coding region is associated with human gastric cancer. This mutation reduced the expression of mature miR-125a and alleviated its inhibitory effect on erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene expression and on gastric tumor cell proliferation. Thus, the data of this study suggested that this germline mutation in pri‑miR-125a likely contributes to the genetic predisposition to gastric cancer by reducing the production of miR-125a, thereby interfering with the expression of miR-125a target genes.