Response surface methodology (RSM) based on Box-Behnken design was successfully applied to the optimization of the operating conditions in decolorization of acid green 20 (AG 20) by ultrasonic irradiation in the presence of H(2)O(2). The effects of three operating variables, ultrasonic power density, initial pH value of dye solution and H(2)O(2) concentration on the decolorization efficiency of AG 20 were evaluated. A quadratic model for AG 20 decolorization was proposed. Analysis of variance (ANOVA) indicated that the proposed quadratic model could be used to navigate the design space. The proposed model was approximately in accordance with the experimental case with correlation coefficients R(2) and R(adj)(2) of 0.9995 and 0.9984, respectively. The optimum operating conditions for AG 20 decolorization were found to be 1.08 W/mL of ultrasonic power density, 4.85 of initial pH and 1.94 mM of H(2)O(2) concentration, respectively. The predicted decolorization rate under the optimum conditions determined by RSM was 96.8%. Confirmatory tests were carried out under the optimum conditions and the decolorization rate of 96.3% was observed, which closely agreed with the predicted value. The results confirmed that RSM based on Box-Behnken design was an accurate and reliable method to optimize the operating conditions of AG 20 decolorization.