The effect of high hydrostatic pressure (HHP) treatment and heat treatment on the stability of Agaricus bisporus mushroom polyphenoloxidase (PPO) was studied. Residual activities of the PPO were investigated after HHP treatment at 100~1600MPa for 0.2~25min and heat treatment at 55~80℃ for 0.2~20min. The HHP and heat inactivation kinetic of mushroom PPO were analyzed by first-order and biphasic model. The results showed that the effect of inactivation was improved with the pressure and temperature increasing, as well as the treatment time increasing. The residual activities were all higher than 88% when treated at pressure lower than 600 MPa, indicated that treatment at pressure lower than 600 MPa had limited influence on the activity of PPO. After HHP treatment at 800, 1000, 1200, 1400 and 1600MPa for 25min, the residual activity reduced to 66.42%, 52.83, 27.20%, 2.20% and 0.01%, respectively. The first-order model was used to analyze the survival curves of heat treatment. All of the coefficients of determination (R2) were higher than 0.960, which proved that the first-order model fit the microbial inactivation kinetics curve well. However, as R2 were all higher than 0.982, the biphasic model was proved to be more suitable than the first-order model to describe the kinetics of PPO inactivation treated by HHP.