As　the　activator　of　hepatocyte　growth　factor　(HGF),　hepatocyte　growth　factor　activator　(HGFAC)　has　been　previously　reported　to　involve　in　liver,　kidney,　and　stomach　regeneration　in　response　to　injury　and　several　types　of　cancers.　This　study　aimed　to　explore　the　expression　of　HGFAC　and　the　correlation　between　decreased　HGFAC　and　DNA　methylation　in　liver　cancer　and　its　clinical　significance.　The　molecular　profiling　of　HGFAC　in　liver　cancer　was　analyzed　using　genomic,　transcriptomic,　immunohistochemistry,　and　patient　survival　information　from　databases,　including　oncomine,　HPA,　COSMIC,　UCSC　Xena,　MPRESS,　and　Kaplan-Meier　plotter.　It　was　found　that　HGFAC　expression　at　transcriptional　and　translational　level　decreased　in　liver　cancer　compared　with　normal　tissues.　There　is　a　negative　correlation　between　the　HGFAC　expression　and　methylation　around　the　promoter　region　which　indicated　that　HGFAC　expression　might　be　controlled　by　DNA　methylation.　Moreover,　the　decreased　HGFAC　is　associated　with　significantly　short　over　survival　time　in　liver　cancer　patients.　In　conclusion,　decreased　HGFAC　expression　in　liver　cancer　associated　with　poor　survival　outcome.　Hypermethylation　around　the　promoter　region　contributed　to　the　decreased　expression　of　HGFAC.　HGFAC　may　be　a　useful　and　predictive　biomarker　for　the　prognosis　of　liver　cancer　patients.　To　the　best　of　our　knowledge,　this　is　the　first　report　describing　the　relationship　between　HGFAC　DNA　methylation　and　its　expression.