Rhodamine B (RhB) dye is studied as target pollutant in this work due to its various adverse effects on skin, gastrointestinal and respiration systems. In the present study, decolorization of RhB dye by sonophotocatalysis (SPC) method in a synthetic aqueous solution was investigated using a hybrid laboratory-scale, batch-mode reactor system with a pure, nano-sized catalyst under ultraviolet A (UVA) light (~365 nm) irradiation for 90 minutes. To achieve maximum RhB decolorization, independent parameters which were TiO2 concentration (0.5 to 2.5 g/L), initial pH (2 to 10) and concentration of RhB (10 to 50 mg/L), were chosen in this method. The three-level Box-Behnken factorial design (BBD) was selected to carry out the optimization method. The finding results presented that TiO2 concentration of 0.5 g/L, pH 2, and an initial RhB concentration of 15.25 mg/L were optimum parameters to achieve maximum RhB decolorization. Further, lamp type, lamp electrical power, and adding H2O2 that could affect the removal efficiency were investigated as a first time. Based on ANOVA analysis, concentration of RhB stated the most significant effects followed by pH and TiO2 concentration on the model. A good compliance between experimental results and predictive values were obtained by the regression analysis for the model with R2 value of 0.9902. The results showed that the Langmuir–Hinshelwood (L-H) model could clarify the SPC process well, where kc and KLH were 0.941 mg/Lmin and 0.129 L/mg, respectively.