Glioblastoma　multiforme　(GBM)　is　the　most　lethal　glioma　variant　in　the　adult　brain　and　among　the　deadliest　of　human　cancers.　Increasing　evidence　has　shown　that　metabotropic　glutamate　receptor　subtype　4　(mGluR4)　expression　may　play　roles　in　regulating　the　growth　of　neural　stem　cells　as　well　as　several　cancer　cell　lines.　Here,　we　investigated　the　effects　of　mGluR4　on　the　growth　and　apoptosis　of　the　LN229　GBM　cell　line.　Involvement　of　Gli-1,　one　of　the　key　transcription　factors　in　the　sonic　Hedgehog　(SHH)　signaling　pathway,　was　further　explored.　In　this　study,　mGluR4　was　activated　using　selective　agonist　VU0155041;　and　gene-targeted　siRNAs　were　used　to　generate　loss　of　function　of　mGluR4　and　Gli-1　in　LN229　cells.　The　results　demonstrated　that　LN229　cells　expressed　mGluR4　and　the　agonist　VU0155041　decreased　cell　viability　in　a　dose-　and　time-dependent　manner.　Activation　of　mGluR4　inhibited　cyclin　D1　expression,　activated　pro-caspase-8/9/3,　and　disrupted　the　balance　of　Bcl-2/Bax　expression,　which　indicated　cell　cycle　arrest　and　apoptosis　of　LN229　cells,　respectively.　Furthermore,　Gli-1　expression　was　reduced　by　mGluR4　activation　in　LN229　cells,　and　downregulation　of　Gli-1　expression　by　gene-targeted　siRNA　resulted　in　both　inhibition　of　cell　proliferation　and　promotion　of　apoptosis.　Moreover,　VU0155041　treatment　substantially　blocked　SHH-induced　cyclin　D1　expression　and　cell　proliferation,　while　increasing　TUNEL-positive　cells　and　the　activation　of　apoptosis-related　proteins.　We　concluded　that　activation　of　mGluR4　expressed　in　LN229　cells　could　inhibit　GBM　cell　growth　by　decreasing　cell　proliferation　and　promoting　apoptosis.　Further　suppression　of　intracellular　Gli-1　expression　might　be　involved　in　the　action　of　mGluR4　on　cancer　cells.　Our　study　suggested　a　novel　role　of　mGluR4,　which　might　serve　as　a　potential　drug　target　for　control　of　GBM　cell　growth.