As one of the most popular and deadly malignant tumors, gastric cancer still has difficulty in early-diagnosis. Recently the level of circulated DNA related with tumors can be used for diagnosis. MicroRNA-421 (miR-421) has been found to be up-regulated in tumor cells. Whether peripheral miR-421 can be used as a marker for diagnosis of gastric carcinoma, however, remains unclear. The expression level of miR-421 in both gastric cancer and normal people were firstly quantified. We then performed in vitro transfection of gastric carcinoma cell line to potentiate or silence miR-421 level. Cell apoptosis and apoptotic protein levels were quantified by flow cytometry and Western blotting, respectively. MiR-421 level in the peripheral blood of gastric cancer patients was significantly elevated. In gastric cancer cell line, the up-regulation of miR-421 significantly inhibited cell apoptosis. The silencing of miR-421 promoted cell apoptosis. Such anti-apoptotic role of miR-421 was accomplished by inhibiting caspase 3, upregulating Bcl-2 and inhibiting Bax. MiR-421 was up-regulated in both tumor tissue and peripheral blood, and can modulate cell apoptosis. Circulated miR-421 can work as a serological marker for early diagnosis of gastric cancer.