As a matter of fact in high-precision positioning systems, flexible hinges are crucial elements for flexure based mechanisms. In this study, the optimal design solution and fatigue life prediction of a flexible mechanism are proposed. Based on pseudo-rigid-body model (PRBM) and the Castigliano's theorem, two formulated mathematic models are taken into consideration as two objectives. These objectives are optimized simultaneously via combining a fuzzy reasoning with Taguchi method. The results indicated that the optimal hinge shape includes a length of 55 mm, a width of 30 mm and a thickness of 1.2 mm. Analysis of variance showed that the thickness of a proposed hinge is the most significant parameter, with a contribution of 66.41%. And then, the fatigue life predictive model is formulated as a further effective tool for flexure based mechanisms. The hybrid methodology in the current paper is usefully expected for flexible manipulators.