As　a　key　factor　in　cellular　metabolic　processes,　nitric　oxide　(NO)　is　a　challenging　target　for　in　situ　real-time　monitoring　due　to　its　transient　property　and　short　diffusion　distance.　Scanning　electrochemical　microscopy　(SECM)　has　unique　advantages　in　single-cell　analysis,　which　can　obtain　the　electrochemical　current　by　scanning　the　cell　surface　with　a　tip　microelectrode.　In　particular,　it　can　further　improved　the　electrochemical　response　by　enhancing　the　interface　properties　of　its　tip.　Here,　an　interface　design　strategy　based　on　platinum　single　nanoparticle　(Pt　NP)　was　developed,　and　fluorinated　self-assembled　monolayers　(SAMs)　were　used　to　further　improve　its　performance.　This　modified　tip　was　used　as　an　SECM　probe　for　NO　concentration　monitoring　and　morphological　imaging　of　single　MCF-7　cells.　It　has　the　high　sensitivity　(164.7　μA/μM·cm2)　and　good　selectivity　for　NO　detection,　which　benefits　from　the　efficient　catalytic　properties　of　Pt　NPs　and　high　mass　transport　and　hydrophobic　antifouling　properties　of　the　interface.　Notably,　it　shows　a　superior　performance　in　detecting　the　fluctuation　of　NO　released　by　a　single　MCF-7-cell　under　the　stimulation　of　cadmium　(Cd),　which　demonstrates　a　promising　method　for　using　a　single-particle-based　tip　in　SECM　applications.　©　2022　Elsevier　B.V.