The set pressure in pressure relief valves (PRVs) varying with the type of sealed medium has been a puzzling problem in the field of chemical machinery and equipment for many years. Here we propose a novel viewpoint to interpret this phenomenon, by which the set pressure difference is ascribed to the additional adsorption pressure of sealed medium adsorbed in the intrinsic nanoscale apertures of PRVs. To demonstrate, two individual types of medium gases (i.e., saturated steam and air) sealed in different PRVs are investigated, and upon a multiscale model of the apertures in PRVs, the additional adsorption pressures are evaluated by using classical density functional theory (DFT). Our calculation shows that the adsorption force of steam is always higher than that of air, resulting in a lower set pressure disregarding the use of different PRVs. The theoretical results are compared with the experimental measurements, displaying qualitatively good agreement, which supports our surmise. Finally, possible solution to reduce the set pressure difference is discussed. This work cast helpful insights for the design and application of PRVs. (C) 2018 Elsevier Ltd. All rights reserved.