The combination of sonolysis and photolysis in the presence of hydrogen peroxide (H2O2) in a 7-L external-loop airlift sonophotoreactor was used to treat the aqueous solution of p-aminophenol. The central composite design (CCD) and response surface methodology (RSM) were employed to evaluate the interaction effects of the initial H2O2 concentration (x(1) = 100-900 mg/L), the ultrasonic power (x(2) = 25-65W), the air flow rate (x(3) = 1-5 L/min), and the initial concentration of p-aminophenol (x(4) = 10-50 mg/L) on the p-aminophenol degradation and total organic carbon (TOC) reduction efficiencies as well as to optimize operating conditions. The coefficients of determination (R-2) and adjusted-R-2 obtained from the analysis of variance (ANOVA) were 0.9900 and 0.9812 for the p-aminophenol degradation; and 0.9742 and 0.9516 for the TOC removal, respectively, ensuring a satisfactory adjustment of the quadratic regression model with experimental results. The linear, square, and interaction effects of x(1), x(2), x(3), and x(4) were also calculated. Genetic algorithm optimization was employed to maximize the mineralization efficiency. 79% TOC reduction efficiency after 90 min and 86.5% p-aminophenol removal efficiency after 30 min were achieved under recirculating batch mode at operating conditions of x(1) = 740 mg/L, x(2) = 65W, x(3) = 5 L/min, and x(4) = 24 mg/L. (C) 2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.