Enzyme-based nanobiohybrids (EnNBHs) are an emerging biocatalyst family that can manufacture industrial products such as fuels and chemicals in a green and low- carbon manner. Designing high-performance EnNBHs could confer enzymes with superior robustness and durability, while current strategies confront grand challenges. Indeed, the reticular chemistry materials, especially metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bond organic frameworks (HOFs), are several good candidates for constructing EnNBHs. While, MOFs and HOFs are constructed by coordination bond and hydrogen bond, respectively, which may be destroyed by acid or organic solvents, thus causing structural degradation and loss of protection to enzymes. The use of acetic acid (6 mol L-1) and organic solvents is conventional conditions for the synthesis of COFs, which may be inapplicable for de novo constructing EnNBHs. Herein, a facile and versatile in situ entrapment strategy is developed to entrap a series of enzymes in crystalline imine-based covalent organic networks (CONs) under mild conditions. Notably, the growth rate of CONs induced by glucose oxidase (GOx) is increased by 2 folds than that of CONs in the absence of GOx. Moreover, the crystalline CONs could create confinement environment and safeguard the hosted enzymes from being denatured under unfavorable conditions. Given moderate crystallinity of CONs, short-range ordered micro/meso-porous structures are generated. Compared with GOx@ZIFs, the larger transport channels for reactants/products in GOx@CONs result in 1.73-fold enhancement in the catalytic efficiency. The crystalline CONs could also serve as a cell-mimic nanoreactor for multienzyme catalysis, demonstrating the potential applications in biomanufacturing, bioimaging, biosensing and so on.