OBJECTIVE: MicroRNAs (miR-NAs) affect almost all cell behaviors of human cancers including gastric cancer (GC). However, the biological role of miR-411 in GC remains to be elucidated. MATERIALS AND METHODS: We determined the expression level of miR-411 in GC cell lines. After synthetic miRNAs or SET domain containing 6 (SETD6) expression vectors transfection, cell proliferation, colony formation, and migration were examined. Moreover, the target of miR-411 was identified by luciferase activity reporter assay and Western blot assay. RESULTS: Results revealed that the miR-411 expression was significantly down-regulated in GC cell lines compared with normal colonic epithelial cells. Overexpression of miR-411 inhibits GC cell proliferation, colony formation, and migration, whereas the overexpression of SETD6 promotes cell proliferation, colony formation, and migration. Moreover, SETD6 was identified as a putative target of miR-411. In addition. we showed miR-411 regulates GC cell behaviors by targeting SETD6. The overexpression of SETD6 promoted the activation of the nuclear factor (NF)-kappa B signaling pathway. CONCLUSIONS: These results suggested that miR-411 functions as a tumor suppressor in GC through targeting SETD6/NF-kappa B pathway. Targeting miR-411 may be a novel clue for GC treatment.