Cancer　cell　metastasis　is　a　major　cause　of　cancer　death.　Unfortunately,　the　underlying　molecular　mechanisms　remain　unknown,　which　results　in　the　lack　of　efficient　diagnosis,　therapy　and　prevention　approaches.　Nevertheless,　the　dysregulation　of　the　cancer　cell　secretome　is　known　to　play　key　roles　in　tumor　transformation　and　progression.　The　majority　of　proteins　in　the　secretome　are　secretory　proteins　and　membrane-released　proteins,　and,　mostly,　the　glycosylated　proteins.　Until　recently,　few　studies　have　explored　protein　N-glycosylation　changes　in　the　secretome,　although　protein　glycosylation　has　received　increasing　attention　in　the　study　of　tumor　development　processes.　Here,　the　N-glycoproteins　in　the　secretome　of　two　human　hepatocellular　carcinoma　(HCC)　cell　lines　with　low　(MHCC97L)　or　high　(HCCLM3)　metastatic　potential　were　investigated　with　a　in-depth　characterization　of　the　N-glycosites　by　combining　two　general　glycopeptide　enrichment　approaches,　hydrazide　chemistry　and　zwitterionic　hydrophilic　interaction　chromatography　(zic-HILIC),　with　mass　spectrometry　analysis.　A　total　of　1,213　unique　N-glycosites　from　611　N-glycoproteins　were　confidently　identified.　These　N-glycoproteins　were　primarily　localized　to　the　extracellular　space　and　plasma　membrane,　supporting　the　important　role　of　N-glycosylation　in　the　secretory　pathway.　Coupling　label-free　quantification　with　a　hierarchical　clustering　strategy,　we　determined　the　differential　regulation　of　several　N-glycoproteins　that　are　related　to　metastasis,　among　which　AFP,　DKK1,　FN1,　CD151　and　TGF　beta　2　were　up-regulated　in　HCCLM3　cells.　The　inclusion　of　the　well-known　metastasis-related　proteins　AFP　and　DKK1　in　this　list　provides　solid　supports　for　our　study.　Further　western　blotting　experiments　detecting　FN1　and　FAT1　confirmed　our　discovery.　The　glycoproteome　strategy　in　this　study　provides　an　effective　means　to　explore　potential　cancer　biomarkers.