Photoacoustic　imaging-guided　photothermal　therapy　in　the　second　near-infrared　(NIR-II)　window　shows　promise　for　clinical　deep-penetrating　tumor　phototheranostics.　However,　ideal　photothermal　agents　in　the　NIR-II　window　are　still　rare.　Here,　the　emeraldine　salt　of　polyaniline　(PANI-ES),　especially　synthesized　by　a　one-pot　enzymatic　reaction　on　sodium　bis(2-ethylhexyl)　sulfosuccinate　(AOT)　vesicle　surface　(PANI-ES@AOT,　λmax ≈　1000 nm),　exhibits　excellent　dispersion　in　physiological　environment　and　remarkable　photothermal　ability　at　pH　6.5　(photothermal　conversion　efficiency　of　43.9%).　As　a　consequence　of　the　enhanced　permeability　and　retention　effect　of　tumors　and　the　doping-induced　photothermal　effect　of　PANI-ES@AOT,　this　pH-sensitive　NIR-II　photothermal　agent　allows　tumor　acidity　phototheranostics　with　minimized　pseudosignal　readout　and　subdued　normal　tissue　damage.　Moreover,　the　enhanced　fluidity　of　vesicle　membrane　triggered　by　heating　is　beneficial　for　drug　release　and　allows　precise　synergistic　therapy　for　an　improved　therapeutic　effect.　This　study　highlights　the　potential　of　template-oriented　(or　interface-confined)　enzymatic　polymerization　reactions　for　the　construction　of　conjugated　polymers　with　desired　biomedical　applications.　©　2020　Wiley-VCH　GmbH