Although research on photodynamic therapy (PDT) of malignant tumor has made considerable progress in recent years, it is a remaining challenge to extend PDT to the second near-infrared window (NIR-II) along with real-time and accurate NIR-II fluorescence imaging to determine drug enrichment status and achieve high treatment efficacy. In this work, lanthanide nanoparticles (Ln NPs)-based nanoplatform (LCR) equipped with photosensitizerChlorin e6 (Ce6) and targeting molecular NH2-PEG1000-cRGDfK aredeveloped, which can achieve NIR-II photodynamic therapy (PDT) and NIR-II fluorescence imaging by dual channel excitation. Under 808nm excitation, Nd3+ in the outer layer can absorb the energy and transfer inward to emit strong NIR-II emissions (1064 and 1525nm). Due to the low background noise of NIR-II light and the targeting effect of NH2-PEG1000-cRGDfK, LCR can recognize tiny tumor tissue (≈3mm) and monitor drug distribution in vivo. Under 1530nm excitation, internal Er3+ can be self-sensitized, generating intense upconversion emission (662nm) that can effectively activate Ce6 for in vivo PDT due to the deep tissue penetration of NIR-II light. This study provides a paradigm of theranostic nanoplatform for both real-time fluorescence imaging and PDT of orthotopic breast tumor in NIR-II window.