C-terminal　binding　protein　2　(CtBP2)　is　a　transcriptional　co-repressor　that　promotes　cancer　cell　migration　and　invasion　by　inhibiting　multiple　tumor　suppressor　genes　that　contribute　to　cell　mobility　and　adhesion.　In　this　investigation,　we　showed　thatCtBP2　expression　was　increased　significantly　in　HCC　tissues　when　compared　to　matched　normal　adjacent　liver　tissues.　We　also　showed　that　CtBP2　expression　is　associated　with　worse　HCC　patient　prognosis　after　liver　resection.　CtBP2　overexpression　induced　epithelial-mesenchymal　transition　(EMT)　in　Huh7　cells　and,　correspondingly,　silencing　CtBP2　suppressed　EMT　in　MHCC97H　cells.　ChIP　assays　revealed　that　GLI1　increased　CtBP2　transcription　by　directly　binding　its　promoter.　Furthermore,　interaction　of　CtBP2　and　Snail　Family　Zinc　Finger　1　(SNAI1),　both　of　which　were　found　to　be　positively　regulated　by　GLI1,　was　confirmed　by　Co-IP　assay.　SNAI1　knockdown　revealed　that　SNAI1　was　essential　for　CtBP2　induction　of　the　EMT　phenotype　of　HCC　cells,　and　CtBP2　knockdown　reversed　GLI1-SNAI1　driven　EMT　in　Huh7　cells.　Finally,　in　vivo　experiments　demonstrated　that　enhanced　CtBP2expression　promoted　HCC　xenograft　growth　and　induced　EMT.　In　conclusion,　CtBP2　may　serve　as　a　prognostic　marker　for　post　liver　resection　HCC　and　may　play　a　role　during　GLI1-driven　EMT　as　a　transcriptional　co-repressor　of　SNAI1.