We describe a one-pot synthesis of novel large-pore mesoporous silica nanoparticles using a nonsurfactant template, tannic acid, and protein immobilization on these particles. The tannic-acid-templated mesoporous silica nanoparticles (TA-MSNPs) possess tunable large pores (6–13 nm), unique pore morphology, and a uniform diameter of ca. 200 nm. TA-MSNPs show high protein adsorption capacity of 77.1 mg/g for lysozyme, 396.5 mg/g for bovine hemoglobin, and 130.0 mg/g for bovine serum albumin and rapid protein uptake. They can also adsorb a large amount of m-MDH (421 ± 13 mg/g) and protect this enzyme from the environment, as demonstrated by its high activity when encapsulated inside the mesopores of TA-MSNPs.