Controlling excitation and emission wavelengths on demand is very significant in bioimaging. Up-conversion nanoparticles (UCNPs) emit visible light upon near-infrared (NIR) light excitation and are well studied in bioimaging. Red emission is usually preferred to green due to its higher tissue penetration depth in bioimaging. Herein, dominant red emission has been achieved under 808 nm excitation based on the designed α-NaYbF4:Mn(2+)/Er(3+)@NaLuF4:Mn(2+)/Yb(3+)@NaNdF4:Yb(3+)@NaGdF4 (C@S1@S2@S3) nanostructure. The rationally designed interlayer shell NaLuF4:Mn(2+)/Yb(3+) could efficiently filter unwanted energy back-transfer from Er(3+) to Nd(3+) and the outmost shell NaGdF4 could prevent excitation energy from surface-related quenching. The lifetime of (4)F9/2→(4)I15/2 transition of Er(3+) could be as high as 0.7 ms. Moreover, C@S1@S2@S3 UCNPs also possess effective contrast efficiency for both X-ray computed tomography (CT) and magnetic resonance (MR) imaging. The designed multifunctional UCNPs could be used as a potential multimodal bioprobe in bioimaging applications.