Less than a century ago, gastric cancer (GC) was the most common cancer throughout the world. Despite advances in surgical, chemotherapeutic, and radiotherapeutic treatment, GC remains the number 3 cancer killer worldwide. This fact highlights the need for better diagnostic biomarkers and more effective therapeutic targets. RAB11-FIP2, a member of the Rab11 family of interacting proteins, exhibits potential tumor suppressor function. However, involvement of RAB11-FIP2 in gastric carcinogenesis is yet to be elucidated. In this study, we demonstrated that RAB11-FIP2 was downregulated in GC tissues and constituted a target of the known onco-miRs, miR-192/215. We also showed that functionally, Rab11-FIP2 regulation by miR-192/215 is involved in GC-related biological activities. Finally, RAB11-FIP2 inhibition by miR-192/215 affected the establishment of cell polarity and tight junction formation in GC cells. In summary, this miR-192/215-Rab11-FIP2 axis appears to represent a new molecular mechanism underlying GC progression, while supplying a promising avenue of further research into diagnosis and therapy of GC.