Objective To investigate the effect of gambogic acid (GA) on invasion in human gastric carcinoma SGC-7901 cells and its possible mechanism.  Methods Cell counting kit-8(CCK-8) assay was performed to detect the effects of GA, inhibitor of nuclear factor kappa-B kinase(IKK)16 and 5-fluorouracil (5-FU) on cell activity of GES-1 and SGC-7901 cells. Cell invasion was assessed with Transwell invasion assay. Western blotting was used to analyze the protein levels of vimentin, matrix metalloproteinase 2 (MMP-2) and MMP-9 and protein phosphorylation of IKKα and p65.  Results The cell activity was significantly decreased in SGC-7901 cells treated with GA in a dose-dependent manner with a half inhibiton concentration(IC50) value of 1.89 μmol/L. But GA had no significant influence on cell viability of GES-1 cells. Meanwhile, 5-FU reduced the cell activity of GES-1 and SGC-7901 cells with IC50 values of 7.36 μmol/L and 199.57 μmol/L respectively. Low-dose GA and IKK16 impaired separately the ability of invasion in SGC-7901 cells, and down-regulated the protein levels of MMP-2, MMP-9 and vimentin, and inhibited phosphorylation of IKKα and p65, while a stronger inhibition was showed when the combination of GA and IKK16 was used.  Conclusion Low-dose GA might inhibit invasion of SGC-7901 cells via IKKα/p65 signaling pathway.