Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor.