Tissue　inhibitor　of　metalloproteinase　1　(TIMP-1)　is　an　endogenous　inhibitor　for　MMPs　that　regulates　the　remodeling　and　turnover　of　the　ECM　during　normal　development　and　pathological　conditions.　Intriguingly,　recent　studies　have　shown　that　TIMP-1　plays　a　dual　role　in　cancer　progression.　In　this　study,　we　found　that　TIMP-1　expression　in　HCC　tissues　is　associated　with　advanced　TNM　stage,　intrahepatic　metastasis,　portal　vein　invasion,　and　vasculature　invasion.　Notably,　TIMP-1　expression　in　HCC　tissue　is　significantly　related　to　worse　overall　survival　for　patients　with　HCC　after　liver　resection.　Ectopic　TIMP1　expression　promoted　the　growth　of　HCC　xenografts　in　nude　mice.　Both　co-culture　with　Huh7　cells　with　a　high　level　of　TIMP-1　and　TIMP1　treatment　resulted　in　up-regulation　of　hallmarks　of　carcinoma-associated　fibroblasts　(CAFs)　and　accelerated　cell　proliferation,　migration　and　invasion　in　immortalized　liver　fibroblasts　(LFs)　isolated　from　human　normal　liver　tissue.　By　co-culture　with　CAFs,　SDF-1/CXCR4/PI3K/AKT　signaling　was　activated　and　apoptosis　was　markedly　repressed　with　an　increased　Bcl-2/BAX　ratio　in　Huh7　cells.　Taken　together,　our　observations　suggest　that　TIMP-1　induces　the　trans-differentiation　of　LFs　into　CAFs,　suppresses　apoptosis　via　SDF-1/CXCR4/PI3K/AKT　signaling　and　then　promotes　HCC　progression.　This　protein　may　be　a　potential　prognostic　biomarker　and　therapeutic　target　for　HCC.