Melanoma　is　a　highly　aggressive　malignancy　and　early　monitoring　and　diagnosis　are　challenging　at　present.　Tyrosinase　is　overexpressed　in　melanoma　and　regarded　as　an　important　biological　marker　for　diagnosis　and　treatment.　Thus,　the　selective　and　sensitive　detection　of　tyrosinase　is　of　great　significance.　To　date,　a　few　fluorescent　probes　have　been　reported　for　the　detection　of　tyrosinase　in　vitro　or　in　vivo.　However,　a　highly　sensitive　near-infrared　probe　for　tyrosinase　monitoring　is　still　missing.　In　this　study,　the　Gibbs　free　energy　change　of　different　urea　bonds　during　spontaneous　hydrolysis　is　analyzed　with　the　aid　of　chemical　thermodynamic　computation.　On　the　basis　of　this　analysis,　we　modified　the　dye　methylene　blue　with　a　rationally　designed　urea　bond　to　specifically　create　a　probe,　called　MB1,　for　rapid　detection　of　tyrosinase.　Our　experimental　results　demonstrated　that　MB1　can　serve　as　a　highly　sensitive　near-infrared　responsive　fluorescent　probe　for　the　monitoring　and　bioimaging　of　tyrosinase.　In　addition,　the　activated　MB1　probe　can　effectively　kill　melanoma　cells　by　photodynamic　therapy.　Thus,　the　near-infrared　probe　has　great　potential　for　monitoring　and　treating　melanoma.