Synthetic methods and biocatalytic activities of new classes of heterogeneous biocatalysts by immobilizing flavin-containing monooxygenase on corrugated and nanoporous silica nanospheres are reported. The nanoporous and corrugated silica nanospheres are synthesized by etching silica nanospheres with aqueous KOH solution. The etched nanospheres are proven to have increased surface area, corrugated, cage-like external surfaces, and, most importantly, more accessible and well-suited surfaces to immobilize bigger molecules, such as enzymes. Furthermore, the etched silica nanospheres contain hydrophilic and silanol groups that are conducive for anchoring enzymes. By utilizing the structures of the etched silica nanospheres, effective immobilization of flavin-containing monooxygenase 1 (FMO1) is demonstrated. The FMO1 immobilized etched silica nanospheres have shown efficient and recyclable biocatalytic activity for nicotine oxidation.