Dynamic control of cell-surface interactions with near-infrared (NIR) light is particularly attractive for regeneration medicine and cell-based therapy. Herein we successfully achieve NIR-controlled cell adhesion with upconversion nanoparticles (UCNPs) based programmable substrate. The UCNPs can harvest the biocompatible NIR light and convert it into local UV light, which results in cleavage of the photocaged linkers and on-demand release of adhesive cells. The strategy also enables the feasibility of deep-tissue photocontrol of cell adhesion on substrate. Our work may open a new avenue for design of UCNP-based cell scaffolds to dynamically manipulate cell-matrix and cell-cell interactions.