The previous experimental results for effect of high pressure and mild heat on Staphylococcus aureus in milk using response surface methodology showed that the optimum process parameters for six log-cycles reduction of S. aureus were obtained as: temperature, 34.4 degrees C; pressure, 329.8 MPa; pressure holding time, 15.5 min. Based on the results, response surface methodology (RSM) was employed in the present work, the effect of food main constituents like soybean protein, sucrose, bean oil and pH of the food matrix on the S. aureus inactivation by high pressure and mild heat was studied, and a quadratic predictive model for the effect of food constituents and pH of food matrix on S. aureus reduction by high pressure and mild heat was built with RSM accurately. The experimental results showed that the efficiencies of S. aureus reduction in milk and food matrix designed in the present work under the HHP treatment process parameters described above had some differences. The soybean protein (P = 0.0082), sucrose (P < 0.0001), and pH (P = 0.0429) significantly affected reduction of S. aureus, and the effect of bean oil on reduction of S. aureus was not significant (P = 0.2790). The adequacy of the predictive model equation for predicting the magnitude orders of S. aureus reduction was verified effectively by the validation data. (c) 2005 Elsevier Ltd. All rights reserved.