Using thermal processing (TP) treatment (100 ℃, 1–8 min) as a control, the effects of high hydrostatic pressure (HHP, 200–500 MPa, 2.5–20 min) on the microbiological and biochemical characteristics of white shrimp Litopenaeus vannamei were investigated. The results showed that the efficiency of polyphenol oxidase (PPO) inactivation and log reduction of total plate count (TPC) by HHP treatment were all significantly lower than by TP treatment (p < 0.05). The rate of inactivation for TPC and PPO all increased with the increase of HHP pressure and holding time (p < 0.05). The inactivation of PPO was in accordance with a first-order kinetics with the HHP treating time. Hardness of HHP-treated samples at the pressure of 300–500 MPa was higher than TP-treated samples, while the yield loss of HHP treatment was significantly lower than with TP treatment (p < 0.05), long time and high pressure of HHP treatment turned the appearance of shrimps slightly pink.