To increase the stabilization and reliability of piezoresistive pressure sensors working in harsh environments with harsh acids, alkalis, corrosive salts, and other destructive substances such as electrostatic particles and damp, a novel piezoresistive pressure sensor was presented. The innovation of the sensor was that the sensing elements of the sensor were fabricated in the lower surface of a silicon diaphragm and were sealed in a vacuum pressure cavity by silicon-glass bonding process. The work principle of this pressure sensor was introduced. Then, Finite Element Method and ANSYS soft were used to simulate the stress distribution of the diaphragm. Finally, the micro-electro-mechanical System(MEMS) technology was used to fabricate a pressure sensor with the dimension of 1.5 mm×1.5 mm×500 μm. The measurement results by a pressure test platform show that the sensitivity of the sensor is about 20 mV/V-MPa, and its maximum nonlinearity is 2.73% FSS, which meets the requirements of the modern industrial applications.