High Temperature Gas cooled Reactors (HTGRs) are designed to have relatively higher thermal efficiency and enhanced safety & environmental characteristics. It can provide energy for combined production of hydrogen, electricity and other industrial applications. The waste heat available in the HTGR power cycle can also be utilized for desalination of seawater for producing potable water. Desalination is an energy intensive process, so use of waste heat from HTGR certainly makes desalination process more economical. Design of coupling system of desalination plant with HTGR as per the safety design requirement of nuclear desalination plant is very crucial. The paper describes the design of the coupling system of hybrid Multi Effect Desalination-Reverse Osmosis (MED-RO) nuclear desalination plant with HTGR to utilize the waste heat in HTGR is discussed. It also discusses the deterministic safety analysis of the coupling system is presented in detail. The analysis shows that the coupling system meets the acceptance criteria for all the Postulated Initiating Events (PIE's) limited to Design Basis Accident (DBA). © 2010 IEEE.