The near-infrared-II (NIR-II) lanthanide-doped inorganic nanoparticles (NPs) have received considerable attention because of their low photon scattering and autofluorescence for deep tissue penetration. These NIR-II NPs have a "rigid" and physiologically inert crystal lattice (such as NaYF 4 :Yb,Er) and cannot be degraded in vivo, limiting their biomedical applications. Changing the chemical structure to achieve the transition from "rigid" to "soft" crystals is a feasible method for realizing their biodegradable applications. Herein, we developed a type of biodegradable NIR-IIb lanthanide-doped inorganic NPs, Na 3 ZrF 7 :Yb,Er,Ce (NZF). By optimizing the regulation of Na and doping with Ce 3+ , the NIR-IIb down-conversion luminescence (DCL) intensity of NZF NPs increased 37 times compared with Na 3 ZrF 7 :Yb,Er. Additionally, because of their "soft" crystal lattice features, water can destroy their crystal structure, and the degradation products can be excreted from the organs and tissues. Furthermore, NZF NPs exhibit red-emitting up-conversion luminescence (UCL). After surface modifications, we performed the proof of concept in biodegradable bioimaging applications and photodynamic therapy based on their NIR-IIb DCL and red-emitting UCL. These findings will benefit the future biomedical applications of lanthanide-doped inorganic NPs.