Modern systems development becomes more and more complicated due to the need on the ever-increasing capability of the systems. In addition to the complexity issue, safety concern is also increasing since the malfunctions of the systems under development may result in the accidents in both the test and evaluation phase and the operation phase. Those accidents can cause disastrous damages if explosiveness gets involved therein such as in weapon systems development. The subject of this paper is on how to incorporate safety requirements in the design of safety-critical systems. As an approach, a useful system structure using the method of design structure matrix (DSM) is studied while reflecting the need on systems safety. Specifically, the effects of system components failure are analyzed and numerically modeled first. Also, the system components are identified and their interfaces are represented using a component DSM. Combining the results of the failure analysis and the component DSM leads to a modified DSM. By rearranging the resultant DSM, a modular structure is derived with safety requirements incorporated. As a case study, application of the approach is also discussed in the development of a military UAV plane.