Autophagy represents an important cellular response to nanoparticles (NPs), whose modulation holds great promise for developing nanomedicine. Here, we systematically studied cell autophagy responses elicited by the NP-protein corona with diverse protein corona types surrounding NPs with different sizes, shapes, and compositions. We demonstrated that these physicochemical properties of NP-protein coronas exerted a remarkable influence on cell autophagy responses. Particularly, for surface protein type-associated modulation of cell autophagy, we correlated the autophagy level to adsorbed protein type on Fe3O4 NPs. Accordingly, we could modulate cell autophagy in response to various levels of protein adsorption. Our work provides new clues to modulate cell autophagy by rational designing NP-protein complexes, which could aid in further biological and therapeutic applications.