Metal organic frameworks (MOFs) with properties of high specific surface area, tunable porosity, controllable structure, open metal sites and desirable functionality, have been demonstrated as stable, robust, reusable, efficient, and cost effective substrates for biomacromolecule immobilization, which have motivated increasing research interest. Biomacromolecule-MOFs composites have extensive application in improvements of biocatalyst efficiency and promising recyclability, molecular sensing, drug deliver and gene therapy. This review focuses on the progress in the application of MOFs as biomacromolecule immobilization matrix and the method and mode for biomacromolecule immobilization to MOFs substrates. The biomacromolecule can be immobilized on the surface of MOFs by physical absorption or covalent bond, diffuse into the pore of MOFs by functional interactions with the MOF ligand moieties or be encapsulated within framework structure by covalent bond or coordination bond during mineralization of MOFs. The design of highly mesoporous and various functional MOFs and the eco-friendly synthesis of biomacromolecule-MOFs composites will enlarge the application range of MOFs as substrates for biomacromolecule immobilization.