tThis work focuses on modeling and optimization of a sono-assisted photocatalytic decolorization process of a modelpollutant, azo dye C.I. direct red 16 (DR16). In the process, a high temperature thermal decomposition nano synthe-sized titanium dioxide (TD-TiO2) was applied as photocatalyst. Central composite design (CCD) methodology wasused for designing the experiments, modeling and optimization of the process. A quadratic model was establishedto describe dependency of the decolorization efficiency (DE), as the model response, to some effective operationalparameters, i.e. the catalyst dosage, pH and the dye initial concentration. The ANOVA analysis confirmed that all ofthe variables have significant influence on the model response. Under the established optimum conditions, 92.4% DEwas achieved after 45 min; however, to access desirable mineralization efficiency, the process should be continuedup to 120 min. All withdrawn samples from the reaction media during the process showed no antibacterial activity,which indicates safety of the treated effluent for disposal into the environment. Also studies showed that the processproceeds via two parallel branches of photolysis and photocatalysis, where propagation of the ultrasonic waves intothe reaction media plays a vital promoting role on the latter branch.