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Uncertainty is inevitable in any manufacturing process. The uncertainty could be due to the variations in geometry of the part, local stress centralization, crack and so on so forth. These defects could be hidden in the part in despite of detection, and finally lead to distortion, break and premature failure. It is helpful and effective to identify, quantify and control the uncertainty and the related defects through process design, which is the foundation of the whole manufacturing. In this article, a method of reliability-based process design and optimization has been put forward and a case study of a welding process design is presented to demonstrate the applicability of the method.