Gastric cancer (GC) has been recognized as the major reason for global cancer-associated mortality. SEC62 homolog, preprotein translocation factor (SEC62) has been documented to possess carcinogenic functions in cancers, but its influence on GC remains elusive. Present study aimed to uncover the impact and mechanism of SEC62 in GC. We validated the upregulation of SEC62 in GC samples by GEPIA, and revealed its high level in GC cell lines. Functionally, depletion of SEC62 hindered proliferation and encouraged apoptosis in GC cells. Furthermore, we found through Starbase 3.0 and validated that methyltransferase like 3 (METTL3) interacted with SEC62 to induce the m(6)A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2 binding protein 1 (IGF2BP1) on SEC62 mRNA. Moreover, we predicted through miRmap and validated that miR-4429 targeted and inhibited METTL3 to repress SEC62. Rescue assays demonstrated that miR-4429 inhibited GC progression through METTL3/SEC62 axis. Together, our study firstly revealed that miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62, indicating miR-4429 as a promising target for treatment improvement for GC. (C) 2019 Published by Elsevier Inc.