CD39　is　one　of　the　important　nucleotidases　to　adjust　extracellular　adenosine　triphosphate　(ATP)　and　adenosine　diphosphate　(ADP)　concentration.　However,　the　enzyme　mimics　to　simulate　the　activity　of　CD39　still　remains　to　be　explored.　Herein　nitrogen-rich　molybdenum　nitride　(Mo5N6)　nanosheets　are　explored　to　possess　CD39-like　activity,　which　are　able　to　catalyze　the　hydrolysis　of　the　high-energy　phosphate　bonds　(HEPBs)　in　ATP　and　ADP　but　not　the　common　phosphate　bonds　in　adenosine　monophosphate　(AMP).　The　catalytic　hydrolysis　of　the　phosphate　bond　over　Mo5N6-700　nanosheets　is　first　investigated　using　para-nitrophenyl　phosphate　as　the　model　substrate　and　then　the　CD39-like　activity　is　further　explored　and　verified　by　31p　NMR　spectroscopy.　Mo4+　on　the　surface　of　Mo5N6-700　nanosheets　are　the　catalytic　active　sites.　Using　ATP　as　the　model　substrate,　the　Km　and　Vmax　values　of　CD39-like　activity　at　optimal　pH　9.0　are　3.2 µmol　L−1　and　18.5 µmol　L−1　h−1,　respectively.　The　CD39-like　activity　of　Mo5N6-700　nanosheets　enabled　the　down-regulation　of　intracellular　ATP　concentration　to　a　larger　degree　for　cancer　cells　than　normal　cells,　which　makes　Mo5N6-700　nanosheets　a　potential　therapeutic　reagent　for　cancers.　©　2024　Wiley-VCH　GmbH.