In　this　study,　we　employed　in　situ　liquid　cell　transmission　electron　microscopy　(LC-TEM)　to　carry　out　a　new　design　strategy　of　precisely　regulating　the　microstructure　of　large-sized　cocatalysts　for　highly　efficient　energy　harvesting.　This　unique　strategy　was　conducted　by　dynamically　in　situ　monitoring　the　entire　process　of　the　galvanic　replacement　reaction　between　Cu　nanowires　and　Au　ion　solutions　to　reveal　the　detailed　microstructural　evolution　at　the　nanometer　scale,　which　has　never　been　achieved　by　conventional　chemical　methods.　Based　on　the　strategy,　four　kinds　of　cocatalysts　were　designed　and　fabricated,　which　have　typical　structural　characteristics　that　correspond　to　different　reaction　stages.　By　coupling　them　with　ultrafine　photocatalysts　to　construct　photocatalytic　systems,　the　photocatalytic　hydrogen　production　of　the　optimized　system　is　65　times　higher　than　that　of　the　counterpart　photocatalysts,　strongly　demonstrating　the　feasibility　of　the　design　via　in　situ　liquid　cell　TEM.　The　strategy　here　provides　an　innovative　way　to　design　new　kinds　of　catalytic　systems.