Objective To investigate the effect of different gene expression levels of Syntenin on invasion and mi?gration of glioma cells and the underlying molecular mechanisms. Methods Lentiviral RNA interference was used to knockdown the expression of syntenin in U-87 cells. Real-time quantitative PCR was used to detect mRNA expression levels of syntenin . Transwell assay and adhesion assay were used to examine the invasion, migration and adhesion, re?spectively. Western-blot was used to detect the protein expression levels of Syntenin, AKT, p-AKT, and MMP-9. Re?sults The mRNA expression level of Syntenin was greatly reduced in interference group compared with empty vector group (P<0.01). The ability of invasion and migration was much lower in interference group than in empty vector group (P<0.01). However, there were no significant differences in invasion and migration between empty vector group and con?trol group. The adhesion ability of glioma U-87 cells was much higher in interference group than in empty vector group (P<0.05). However, when U-87 cells were seeded on 96-wells coated with HUVEC, the adhesion ability was much lower in interference group than in empty vector group(P<0.05). The protein expression levels of Syntenin, p-AKT, and MMP-9 in interference group were markedly decreased compared with empty vector group(P<0.05). There was no signif?icant difference in expression of AKT protein between interference group and empty vector group (P>0.05). Conclusion Syntenin may enhance the invasion and migration ability of glioma though up-regulation of p-AKT, which in turn pro?motes MMP-9 expression in a corresponding signal transduction pathway.