Big　data　in　healthcare　has　drawn　substantial　attention　in　recent　years.　Current　researches　on　big　data　in　healthcare　are　highly　interdisciplinary　involving　methodologies　from　engineering,　computing,　behavior　science,　information　science,　social　science,　management　science,　as　well　as　many　different　areas　in　medicine　and　public　health.　However,　the　identification　of　major　hot　topics　and　related　research　methodologies　in　big　data　in　healthcare　still　lacks　a　comprehensive　quantitative　analysis.　To　provide　a　better　understanding　of　the　hot　topics　and　methodologies　in　big　data　in　healthcare　and　their　future　trends,　a　systematic　and　comprehensive　literature　search　of　the　published　research　papers　from　past　20　years　in　big　data　research　of　healthcare　was　conducted　and　the　resulting　321　literature　papers　were　reviewed　and　analyzed.　Overall,　we　identified　three　major　topics　comprising　of　omics,　medical　specialties　and　IT　healthcare,　with　13　subtopics.　We　also　classified　the　used　methodologies　into　7　types　relating　to　different　areas.