taking into account, the need for handling clinical information under uncertainty from clinical domain knowledge and clinical data in clinical decision making, we proposed a new Belief Rule Based (BRB) Architectural Framework to design a clinical decision support system (CDSS). It can handle uncertain information to support the clinical decision making process. This paper describes how to design a clinical knowledge base and inference process of a CDSS by using belief rule-based system with an evidential reasoning approach. A case study demonstrates to employ this BRB Architectural Framework in developing CDSS is a reliable novel approach.