Using a photosensitive hybrid hydrogel loaded with upconversion nanoparticles (UCNPs), we show that continuous-wave near-infrared (NIR) light (980 nm) can be used to induce the gel-sol transition and release large, inactive biomacromolecules (protein and enzyme) entrapped in the hydrogel into aqueous solution "on demand", where their bioactivity is recovered. This study is a new demonstration and development in harnessing the unique multiphoton effect of UCNPs for photosensitive materials of biomedical interest.