We investigated the current unsolved problem of short-term enhancement and long-term decay of the luminescence intensity of quantum dots (QDs)-based lightemitting diodes (LEDs) in applications for lighting and displays, and proved that the interface interaction between the QD surface and atmospheres plays a key role in the QD-LED operation process. It is suggested that the initial luminescence enhancement of QD-LEDs would be caused by the QD surface-adsorbed species, such as ligands and gas molecules, rather than QDs themselves, whereas the luminescence decay is correlated to the interface reactions between QDs and photo-generated reactive oxygen species, which leads to formations of sulfate, hydroxide, and oxide compounds after QDs are illuminated by 450 nm blue light in oxygen and water environments according to surface analysis and theoretic thermodynamic calculations. It was also found that involvement of water in the QD-LED operation can cause crystal merging of QDs possibly because of the surface sulfates in the presence of water.