The sulfur-iodine (SI) cycle to produce hydrogen from water requires a HIx multistage distillation column to obtain hyperazeotropic hydriodic acid vapor as a top product that can be afterward decomposed into hydrogen and iodine. To design a HIx multistage distillation column that can be applied to the cycle, its static and dynamic simulation is essentially demanded. A 50NL-H-2/h scale SI test facility to be operated under a pressurized environment has been constructed in Korea. This study focuses on the HIx multistage distillation column (HIxMDC-50L) for the 50NL-H-2/h SI test facility. The HIxMDC-50L was designed and installed in 2013. Based on the design specifications and operation method, the start-up behavior of the HIxMDC-50L has been analyzed using the simulation code "KAERI-DySCo". As a result of the start-up dynamic simulation, it is confirmed that the HIxMDC-50L will advance to the steady state value within 1050 s to fulfill a hydrogen production rate of 50NL-H-2/h. On the other hand, not only the effects of the column design parameters on the progress to a steady state but also the effects of several operation variables on the top product have been evaluated for safely operating the HIxMDC-50L. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.