Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studieshave shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. Thisstudy was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferationand invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those innormal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (gradeIII+IV) . Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of gliomapatients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predictingoverall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion,impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 isan independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it mayfunction as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.