Information storage in vivo will lead to next-generation identification and security authentication. Here, an information storage method was proposed for in vivo application by using a pair of lanthanide-doped nanoprobes (NdNPs and ErNPs) with orthogonal emissions in the second near-infrared window. The information is stored in different fluorescence channels separately, while the selective readout could be realized by simply manipulating excitation wavelengths. The small-animal experiments primarily confirm the applicability of this method in vivo. The binary numbers ″1″ and ″0″ are implanted under the mice's skin, and the corresponding signals ″on″ and ″off″ can be collected by charge-coupled devices under different laser filter combinations. The design of lanthanide-doped probes with the nanoscale features and orthogonal emissions is expected to provide a new strategy for information storage in vivo. The lanthanide materials with excellent down-conversion near-infrared fluorescence performance have shown great application potential in the field of photonics.