We report for the first time a self-produced bubble-template synthesis of La₂O₃:Yb/Er hollow mesoporous spheres (HMSs) through a facile one-step co-precipitation process. The temperature, which determines bubble formation, and the amounts of citric acid and NaOH, which determine dispersibility, are the main factors in the formation of La₂O₃:Yb/Er HMSs. Au nanocrystals (NCs) with a particle size of 9 nm were conjugated to the as-prepared HMSs without adding any organic reagents. It is noted that the up-conversion (UC) luminescence intensity of La₂O₃:Yb/Er@Au was markedly improved by 49.7-fold under low pump power, and the lifetime has been greatly enhanced due to the local field enhancement (LFE) of Au NCs, which effectively prevents the energy transfer from La₂O₃:Yb/Er to Au nanoparticles (NPs). The enhanced properties have been successfully proved by discrete-dipole approximation (DDA) simulation. The as-prepared La₂O₃:Yb/Er@Au HMSs with large surface area (118 m² g⁻¹) and mesoporous feature (2.92 nm in pore size) exhibit good compatibility. In addition, doxorubicin (DOX) release properties and obvious cytotoxicity to MCF-7 tumor cells reveal their potential application as a drug carrier. In particular, the facile and mass-production synthetic strategy may pave the way for the production of a wide class of materials.