While photothermal therapy is widely applied in phototherapy, there are still challenges in developing new generation phototherapy materials with precise diagnostic functions. Here we report the construction of a pH responsive upconversion fluorescence imaging precisely guided photothermal therapy system, namely NaYF4:Yb3+/Er3+@NaYF4@MnO2@Au nanocomposites, which can effectively avoid light damage to non-target tissues. Owing to the fluorescence resonance energy transfer between the upconversion nanocrystal donor and MnO2 and Au acceptor, the upconversion fluorescence is completely quenched. However, in pH 5.3 PBS buffer, MnO2 is gradually broken down, and the upconversion fluorescence is partially recovered, which could be used for upconversion fluorescence imaging to precisely guide photothermal therapy under 980 nm excitation. Simultaneously, due to the absorption of 980 nm excitation light and the emission bands of Er3+ (2H11/2→4I15/2 and 4S3/2→4I15/2 transition), temperature increment of core@shell@MnO2@Au could reach 35.5 °C under 980 nm excitation at 0.8 W cm-2. The core@shell@MnO2@Au nanocomposites are supposed to contribute significantly in the biological applications of photoluminescence imaging and photothermal therapy.