Particles make extensively physical contact with cells after entering the body, which mediate a series of particle-cell interaction processes. These interaction processes induce different physiological responses of cells and indicate the potential biomedical applications of particles. Hence, controlling the particlecell interaction processes have been attracting more and more attentions. Among factors that affect particle-cell interaction processes, regulating particle multiscale structures is the most dominant. To date, numerous principles have been developed, including integrating particles with different physicochemical properties such as size, shape, elasticity and surface chemistry by various preparation technologies, coating particle surface with cell membrane to endow its biomimetic properties, taking advantage of the particle's dimensional effect, etc. In this review, we will highlight recent progresses on these princi ples, and corresponding biomedical applications in drug delivery, immune modulation and tissue engineering. The challenges and perspectives of regulating particle multiscale structures for controlling interaction processes will also be discussed. (C) 2020 Elsevier Ltd. All rights reserved.