The　widespread　use　of　pharmaceuticals　and　personal　care　products　(PPCPs)　in　many　fields　has　brought　convenience　to　human　lives　but　has　also　caused　unavoidable　environmental　pollution　issues.　In　particular,　the　resistance　gene　problem　resulting　from　accumulating　antibiotics　that　cannot　be　fully　absorbed　by　biological　individuals　has　been　a　concern;　thus,　it　is　urgent　to　find　efficient　technologies　to　boost　the　degradation　efficiency　of　antibiotics　in　the　environment.　Here,　an　ε-MnO2　catalyst　was　prepared　by　a　novel　droplet-interface-drying　method　and　utilized　as　a　Fenton-like　catalyst　for　efficiently　degrading　ciprofloxacin　(CIP).　The　ε-MnO2　shell　was　formed　preferentially　at　the　gas–liquid　interface　and　then　continued　to　decompose　into　ε-MnO2　with　abundant　O　vacancies　in　the　air-insulated　microcavity.　The　XPS　result　confirms　that　this　particular　preparation　method　can　regulate　the　content　of　O　vacancies　in　the　material.　Compared　with　ε-MnO2　samples　obtained　by　the　direct　drying　method　(ε-MnO2-B),　the　catalytic　performance　of　ε-MnO2　prepared　by　the　droplet-interface-drying　method　(ε-MnO2-P)　is　significantly　improved.　By　activating　peroxymonosulfate　(PMS)　with　the　ε-MnO2-P　catalyst,　the　CIP　degradation　efficiency　can　reach　84.1%.　The　detection　and　analysis　of　reactive　oxygen　species　(ROS)　in　the　ε-MnO2-P/PMS　oxidation　system　confirms　that　·OH,　SO4·−　and　1O2　are　the　main　ROS　for　CIP　degradation.　This　study　highlights　the　creation　of　miniature　hypoxic　space　to　regulate　the　content　of　O　vacancies　in　ε-MnO2,　providing　a　new　idea　for　the　synthesis　of　other　O-vacancy-rich　materials.　©　2023　by　the　authors.