Quantum dots (QDs) are widely recognized for their exceptional optical and electronic properties, rendering them valuable for diverse applications. However, the surface structure significantly influences their photoluminescence performance, particularly under acidic conditions, where protons can induce QD aggregation and fluorescence quenching. Herein, we propose a strategy relying solely on elaborate ligand engineering to construct proton-resistant QDs, eliminating the need for multilayer bulky coatings. Proton-resistant Ag2Se QDs have been achieved by a synergistic proton defense mechanism: electrostatic shielding and proton trapping. Specifically, introducing surface ligands with groups that become highly positively charged upon protonation (e.g., amino groups) and employing solvents with low dielectric constants (e.g., ethylene glycol) enhances electrostatic shielding. Furthermore, incorporating abundant hydrogen-bond donors/acceptors into the ligand structure promotes the formation of hydrogen-bonding networks that trap penetrating protons. This hierarchical proton defense, realized purely via precisely designed ligands, enables modified GSH-capped Ag2Se QDs to retain stable fluorescence at proton concentrations up to 0.8 mol/L, exhibiting a four-orders-of-magnitude enhancement in proton tolerance compared to conventional mercaptopropionic acid-capped QDs. This work provides a universal paradigm for designing proton-resistant QDs and advances nanomaterial engineering for harsh environments.