The demand from customers on better products and systems seems to be ever increasing. To meet the demand, the systems are becoming more and more complicated in terms of both scale and functionality, thereby requiring enormous effort in the development. One bright spot of this trend is that such effort has been the driving forces of the remarkable advancement in modern systems development. On the other hand, safety issues appear to be critical in many large-scale systems such as transportation and weapon systems including high-speed trains, airplanes, ships, missiles/rockets launchers, and so on. Such systems turn out to be prone to a variety of faults and thus the resultant failure can cause disastrous accidents. For the reason, they can be referred to as safety-critical systems. The systems failure can be attributed to either random or systemic factors (or sometimes both). The objective of this paper is on how to reduce potential systemic failure in safety critical systems. To do so, a proper system design is pursued to minimize the risk of systemic failure. A focus is placed on the fact that complex systems have a lot of complicated interfaces among the system elements. To effectively handle the sources of hazards at the complicated interfaces and resultant failure, a method is developed by utilizing a design structure matrix. As a case study, the developed method is applied in the design of train control systems.