This paper presents a versatile approach for the synthesis of ultrathin (ca. 10 nm thickness) and bioresponsive protein capsules. The protein capsules are obtained after covalent cross-linking with Lomant's reagent of a single protein layer immobilized onto bromoisobutyramide-modified silica particles, followed by template removal. The combination of protein immobilization and cross-linking steps, affords protein capsules with enhanced mechanical stability and permits the formation of smaller capsule sizes (ca. 200 nm size) without loss of protein biofunctionality, as demonstrated through enzymatic catalysis experiments. Furthermore, we show the facile functionalization of these protein capsules with an anticancer drug, doxorubicin, which is releasable upon exposure to biological stimuli either via reductive cytosolic conditions or protease degradation. These bioresponsive and functionalized protein capsules are likely to have potential in cell targeting, and as drug delivery vehicles and biocatalysts.