Silicon-based piezoresistive pressure sensors suffer from insufficient reliability and reduced service life due to issues such as output drift and sensitivity degradation in harsh environments. This study aims to systematically elucidate the physical mechanisms of stability degradation and to develop a high-precision life prediction model. Utilizing the failure physics analysis theory, it adopted variable-amplitude cyclic loading and accelerated fatigue testing methods to conduct accelerated tests by applying alternating pressure with different amplitudes. It established a dataset of sensor failure degradation through microscopic examination and performance monitoring, and overcame the challenge of analyzing the coupled effects of multiple mechanisms, including diaphragm cracking, piezoresistor creep, and packaging stress failure, ultimately constructed a life prediction model under uniaxial pressure loading conditions. Accelerated life testing demonstrated that under a pressure load of 140% of the full-scale range, the sensor's linearity increased by over 50% after approximately 2.2 million cycles, which is defined as failure. The developed model achieved an error of less than 15% between the predicted and measured lifespan, enabling effective prediction of the sensor's failure cycle. This study holds significant theoretical and practical application value, providing crucial support for advancing the design optimization and lifetime prediction of highly reliable silicon-based pressure sensors.