Safety requirements and design considerations are examined for a nuclear hydrogen production system that consists of High Temperature Gas-cooled Reactor (HTGR) and a hydrogen production plant by thermochemical water splitting iodine-sulfur process (IS process). Requirements in order to construct hydrogen production plants under conventional chemical plant regulation are identified in order to take into account a fundamental difference in safety philosophy between the nuclear facility and chemical plant and meet requests from the potential users of nuclear heat. In addition, safety requirements for the collocation of the nuclear facility and hydrogen production plant utilizing IS process (IS plant) are investigated. Furthermore, design considerations to comply with the requirements are suggested and the technical feasibility of the design considerations is evaluated. The evaluation results for a reference plant showed that safe distance determined by the chemical plant regulation against combustible gas and hazardous chemical leakages comply with the plant layout design. Furthermore, the results demonstrated the feasibility of IS plant construction under non-nuclear regulation by showing that the tritium concentration in IS plant can be maintained below the regulation limit and reactor normal operation can be achieved during abnormal conditions in the IS plant. These results clarified that design considerations suggested for coupling the IS plant to HTGR are reasonably practicable. The proposed criteria can be used not only for coupling hydrogen production plants but also for other chemical plants such as steam reforming plants, etc. (C) 2014 Elsevier Ltd. All rights reserved.