Due to the evolution of war fields to the net-centric one, weapon systems have become very complex in terms of both mission capability and implementation scales. In particular, the net-centric war field is characterized by a set of interconnected and independently operable weapon systems. As such, the individual weapon systems are required to meet the interoperability and thus, assuring it has been becoming more crucial even in the early stage of development. Furthermore, the ever-growing complexity of the weapon systems has attracted a great deal of attention on the safety issues in the operation and development of weapon systems. The objective of the study is on how to assure the interoperability for safety-critical weapon systems while maintaining system complexity. To do so, the approach taken in the paper is to consider the interoperability from the early stage of the development. Specifically, the required functions to satisfy the interoperability are developed first. The functions are then analyzed in order to link the safety requirements to the reliability evaluation, which results in the study of quantifying the effects of the safety requirements on the system as a whole. As a result, we have developed a methodology and procedure on how to assure interoperability while applying the safety requirements in the weapon systems development.