Efficient　catalytic　hydrolysis　of　carbonyl　sulfide　(COS)　into　easy-to-handle　products　is　crucial　for　mitigating　energy　and　environmental　issues.　However,　currently　investigated　catalysts　are　face　the　inherent　problems　of　irreversible　sulfation　and　carbonization　during　the　catalytic　reaction,　making　them　limit　in　industrial　application.　Herein,　we　report　a　simple　and　practical　method　to　synthesize　isolated　Cu–N4　site　on　holey　nitrogen-modified　carbon　nanomeshes　that　can　intensely　resist　sulfur　poisoning　with　a　good　performance　in　COS　hydrolysis.　The　representative　Cu–N4/NC　achieves　a　COS　elimination　of　nearly　100%　and　a　turnover　frequency　(TOF(Cu))　of　12.9　h−1　at　70　°C.　Importantly,　Cu–N4/NC　exhibits　high　long-term　stability,　with　no　obvious　decline　of　hydrolysis　activity　in　the　run　of　32　h,　outperforming　most　of　the　reported　catalysts.　The　isolated　Cu　center　can　effectively　modulate　the　adsorption　and　desorption　of　sulfur　intermediates　and　thus　avoid　the　sulfur　poisoning　of　catalysts　owing　to　its　unique　geometric　structure　and　electronic　properties.　The　in　situ　characterization　demonstrates　that　isolated　Cu–N4　site　can　effectively　catalyze　the　COS　hydrolysis　via　the　adsorbed　*HSCO2　and　*H　intermediates.　Our　discovery　provides　an　opportunity　to　design　highly　active　and　durability　COS　desulfurization　catalysts　with　potential　for　industrial　application.　©　2023　Elsevier　Ltd