This paper describes the fabrication of a highly efficient, non-cytotoxic drug delivery platform designed for photodynamic therapy (PDT): phospholipid-capped, protoporphyrin IX–loaded and FITC-sensitized mesoporous silica nanocarriers (Lipo-FMSNs/PpIX). After derivatization with folate on the phospholipid-capped FMSNs (denoted fa-Lipo-FMSNs/PpIX, the so-called nanoPDT system), we confirmed the nanoPDT systems' selective targeting of and entry into the folic acid receptor-overexpressed HeLa cells by means of cell viability assessment and confocal microscopic analysis. The decrease in the unfavorable dark toxicity of fa-Lipo-FMSNs/PpIX enabled the delivery of high concentrations of PpIX into cells. Moreover, the cellular uptake of the nanoPDT systems was greater than that of free PpIX. Upon irradiation with visible light, the nanoPDT system generated singlet oxygen efficaciously in aqueous environments—a decisive factor affecting its therapeutic applicability in PDT, demonstrating enhanced in vitro photocytotoxicity. Furthermore, an in vivo study of subcutaneous melanoma in nude mice inoculated with B16F10 cells revealed the capability for the nanoPDT system to mitigate nearly 65% of tumor growth.