Persistent luminescence is an optical phenomenon where solid phosphors can store photoenergy in defects and release the energy by luminescence after stopping excitation.Due to the intriguing optical characteristics,the defect luminescence based persistent phosphors have attracted enormous atten-tion in recent decades,especially in biomedical fields such as biosensing and bioimagin8.Persistent luminescence nanoparticles (PLNPs) can effectively avoid the autofluorescence interference from complex samples or tissues,leading to significantly improved sensitivity in biological analysis.In this review,we summarized the methods to control the optical performance of PLNPs from the perspec-tives of controlled synthesis and defect regulation,and emphasized the close relationship between their optical performance and applications.We further provided a summary about a series of PLNPs nanoprobes designed by our group for biosensing and bioimaging.Our efforts,summarized in this review,will not only open a window for manipulating luminescence in PLNPs,but also further promote the application of PLNPs in biomedicine.