An optimization study was done to optimize the operating conditions for sonocatalytic degradation of Rhodamine B with the presence of titanium dioxide (TiO₂) nanotubes at ultrasonic power of 50 W and frequency of 35 kHz. Three operating variables including initial concentration of Rhodamine B, amount of TiO₂ nanotubes and concentration of hydrogen peroxide (H₂O₂) had been investigated. A central composite design (CCD) was used for response surface modeling to evaluate the combined effect of these variables as well as to optimize the degradation efficiency of Rhodamine B. The optimized condition for the sonocatalytic degradation of Rhodamine B was 61.6 mg/L of Rhodamine B, 2.1 g/L of TiO₂ nanotubes and 8.7 mM of H₂O₂ after 3 h. Under these conditions, the maximum degradation efficiency of 86.5 % was achieved. The proposed second-order regression was successfully derived with a high coefficient of determination (R² = 0.99) value. The significance and adequacy of the model were analyzed using analysis of variance (ANOVA). It was found that all individuals and interactions between three variables had important effects in the sonocatalytic degradation of Rhodamine B.