The control of surfactant adsorption/desorption, a fundamental process in colloid and surface chemistry, is of crucial importance for surfactant recycling and pollution-free waste treatment. Using first-principles simulations, we designed a photoswitchable approach to realize separation of a photoresponsive surfactant from the adsorbate. We chose a 4-butyl-(4'-(3-trimethylammoniumpropoxy)phenyl)azobenzene cation and quartz as the model system of a surfactant and adsorbate, respectively. Through first-principles calculations, we found that the trans isomer of the surfactant tends to assemble on the silica surface, while the cis isomer tends to be detached from the surface and is instead surrounded by water molecules. The chemical origin of the difference arises from the interactions between the surfactant and solvent, which depend on the molecular conformational change and associated redistribution of charges before and after the isomerization. Intriguingly, the interaction energy between the silica surface and the surfactant does not change significantly with the conformational change of the molecule. Meanwhile, an appreciable void space of the cis conformer attributed to the steric hindrance disfavors the assembling of surfactants on the silica surface, and its significant polarity favors the water environment, which prompts its desorption from the surface. The prediction from computations was then validated by experimental results. We expect our proof-of-concept study on the phototriggered separation of azobenzene-derived surfactant from a silica surface to provide an alternative way of achieving stimuli-responsive separation of surfactant from adsorbates.