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Moisture properties such as moisture diffusivity and hygroscopic swelling have been carefully investigated for polymeric materials used on the MEMS-based pressure sensor. An improved TMA/TGA integrated method is used to characterize the hygroscopic swelling property. An analytical moisture diffusion solution is proposed to determine the moisture distribution and consequent hygroscopic induced strain as well as stress. By applying Fick's second law of diffusion, the ldquothermal wetnessrdquo analogous technique is applied to solve moisture absorption/desorption models. The analytical expression for total expansion strain due to hygro-thermo-mechanical coupled effect is implemented using finite element software ANSYS. Finite element predictions reveal the significance of contribution of hygroswelling induced effective stress/strain. Reliability analysis and hygro-thermo-mechanical design for a MEMS-based pressure sensor are performed in accordance with JEDEC preconditioning standard JESD22-A120. A series of comprehensive experimental works and parametric studies were conducted in this paper.