Mineral　scaling　is　one　of　the　major　challenges　for　membrane　distillation　in　concentrating　high-salinity　brine.　This　work　first　investigated　the　characteristic　of　CaSO4　scaling,　then　explored　different　cleaning　reagents　to　evaluate　their　efficiencies　and　mechanisms.　By　analyzing　the　SEM　and　EDX　mapping　images,　the　CaSO4　scaling　process　could　be　divided　into　surface　and　pore　scaling　stages.　Three　cleaning　solutions,　i.e.,　commercial　detergent　(20　%),　EDTA-4Na　(0.05　M),　and　MgCl2　(0.8　M),　were　chosen　for　their　high　CaSO4　solubility　(0.7　g　CaSO4　per　100　g　H2O).　At　the　surface　scaling　stage,　three　cleaning　solutions　exhibited　excellent　removal　of　CaSO4　scaling　with　approximately　similar　96　%　cleaning　efficiencies.　However,　at　the　pore　scaling　stage,　only　the　commercial　detergent　showed　high　efficiency　(89　%).　Such　high　cleaning　efficiency　was　mainly　attributed　to　the　detergent＇s　high　total　dissolved　solids　(salinity),　low　pH,　and　high　diffusion　rate　(5.46　mu　m　cm(-1)　min(-1))　across　the　membrane.　Moreover,　periodic　cleaning　at　the　surface　scaling　stage　with　the　commercial　detergent　followed　by　drying　throughout　a　43.5　h　continuous　concentration　test　on　an　actual　RO　brine　could　restore　the　PTFE　membrane　performance　completely,　giving　90　%　of　the　total　water　recovery.　This　work　provides　new　insights　into　the　cleaning　mechanism　for　gypsum　scaling　in　a　hydrophobic　porous　membrane.