In this study, a kind of robust monolithic biocatalyst was constructed through shielding enzymes on the surface of cordierite honeycomb (cordierite-H) ceramics with an organosilica layer. In brief, penicillin G acylase, as a typical enzyme, was immobilized on the cordierite-H surface modified with polydopamine. Then, an organosilica layer was formed through the sob gel process with (3-aminopropyl)tetraethoxysilane and tetraethyl orthosilicate. The buffering effect of the organosilica and polydopamine layer as well as the cage effect of the organosilica layer could effectively protect the enzyme from denaturation and detachment, thus significantly improving its structural and, operational stability. A fixed-bed reactor containing the above monolithic biocatalysts was then constructed. The enzyme could retain up to 89.7% of its initial activity after a 195 min reaction at 313 K and 73.1% of its initial activity after 15 reaction cycles. Furthermore, continuous bioconversion of penicillin G potassium was also achieved, with a final product yield of 41.8% after five cycles of reaction.