Rare earth-doped nanoparticles have been widely used in disease diagnosis, drug delivery, tumor therapy, and bioimaging. Among various bioimaging methods, the fluorescence imaging technology based on the rare earth-doped nanoparticles can visually display the cell activity and lesion evolution in living animals, which is a powerful tool in biological technology and has being widely applied in medical and biological fields. Especially in the band of near infrared (700–1700 nm), the emissions show the characteristics of deep penetration due to low absorption, low photon scattering, and low autofluorescence interference. Furthermore, the rare earth-doped nanoparticles can be endowed with the water solubility, biocompatibility, drug-loading ability, and the targeting ability for different tumors by surface functionalization. This confirms its potential in the cancer diagnosis and treatment. In this review, we summarized the recent progress in the application of rare earth-doped nanoparticles in the field of bioimaging and tumor treatment. The luminescent mechanism, properties, and structure design were also discussed. © The Author(s) 2020.