Photodynamic therapy (PDT) is a noninvasive and site-specific therapeutic technique for the clinical treatment of various of superficial diseases. In order to tuning the operation wavelength and improve the tissue penetration of PDT, rare-earth doped upconversion nanoparticles (UCNPs) with strong anti-stokes emission are introduced in PDT recently. However, the conventional Yb3+-sensitized UCNPs are excited at 980 nm which is over-lapped with the absorption of water, thus resulting in strong overheating effect. Herein, a convenient but effective design to obtain highly emissive 795 nm excited Nd3+-sensitized UCNPs (NaYF4:Yb, Er@NaYF4:Yb0.1Nd0.4@NaYF4) is reported, which provides about six times enhanced upconversion luminescence, comparing with traditional UCNPs (NaYF4:Yb, Er@NaYF4). A colloidal stable and non-leaking PDT nanoplatform is fabricated later through a highly PEGylated mesoporous silica layer with covalently linked photosensitizer (Rose Bengal derivative). With as-prepared Nd3+-sensitized UCNPs, the nanoplatform can produce singlet oxygen more effective than traditional UCNPs. Significant higher penetration depth and lower overheating are demonstrated as well. All these features make as-prepared nanocomposites excellent platform for PDT treatment. In addition, the nanoplatform with uniform size, high surface area, and excellent colloidal stability can be extended for other biomedical applications, such as imaging probes, biosensors, and drug delivery vehicles.