Objectives:　Oral　squamous　cell　carcinoma　(OSCC)　is　one　of　the　most　aggressive　head　and　neck　cancers　with　high　incidence.　Multiple　studies　have　revealed　that　long　non-coding　RNAs　(lncRNAs)　play　pivotal　roles　in　tumorigenesis.　However,　the　role　of　long　intergenic　non-protein　coding　RNA　664　(LINC00664)　on　the　progression　of　OSCC　was　still　unclear.　Subjects　and　methods:　In　this　study,　the　expression　of　LINC00664　in　OSCC　tissues　and　cell　lines　was　detected　by　quantitative　real-time　polymerase　chain　reaction　(qRT-PCR).　The　functional　role　of　LINC0664　was　estimated　by　cell　counting　kit-8　(CCK-8),　transwell　assays,　Western　blot　in　vitro,　and　xenograft　tumor　model　in　vivo.　The　regulatory　mechanism　was　investigated　by　RNA-binding　protein　immunoprecipitation　(RIP),　chromatin　immunoprecipitation　(ChIP),　and　luciferase　reporter　assays.　Results:　LINC00664　was　found　to　be　upregulated　in　OSCC　tissues　and　cell　lines　and　was　associated　with　poor　prognosis　of　OSCC　patients.　LINC00664 knockdown　suppressed　OSCC　cell　proliferation,　migration,　invasion,　and　epithelial-mesenchymal　transition　(EMT).　Moreover,　Kruppel　like　factor　9　(KLF9)　enhanced　LINC00664　expression　at　transcription　level.　Interestingly,　LINC00664　upregulated　KLF9　expression　by　sponging　miR-411-5p.　In　addition,　knockdown　of　LINC00664　restrained　tumor　growth　of　OSCC　in　vivo.　Conclusion:　Our　study　identified　the　oncogenic　roles　of　LINC00664　in　OSCC　tumorigenesis　and　EMT　via　KLF9/LINC00664/miR-411-5p/KLF9　feedback　loop,　which　provides　new　perspectives　of　the　potential　therapeutic　target　for　OSCC.　©　2021　Wiley　Periodicals　LLC.