A chemically well-defined Bio Core@Inorganic Shell nanohybrid, which consists of rationally designed DNA molecule core with a size of ∼100 nm and spherical inorganic nanoshell with an overall thickness of ∼10 nm reassembled with exfoliated layered metal hydroxide (MH nanosheets), is prepared. The DNA encapsulation and its release, due to the pH-dependent solubility of the MH nanoshell, plays a crucial role in maximizing the stability of base sequence-manipulated and probe-functionalized DNA molecules with designed information. The present DNA Core@MH Shell nanohybrid can provide wide bioinspired applications converged with nanotechnology, such as an advanced gene delivery system and a biomedical diagnostics, tracing/collection/sensing system for DNA-based information.