In the present study, ultrasonic-assisted Fenton process called sono-Fenton (SF) with low concentration of Fenton reagents was studied via degradation of Direct Blue 71. Influences of seven operational parameters including initial pH (pH 0 ), initial concentration of pollutant (C 0 ), dose of Fenton reagents (C Fe and C H2O2 ), ultrasound irradiation frequency (Fr S ), ultrasound irradiation power (P S ), and treatment time (t SF ) were investigated on the dye removal efficiency (DR). A combined design of experiments consists of full factorial for t SF , and Taguchi for other six parameters was designed, and experiments were conducted in accordance with the design. The experimental data were collected using a batch reactor equipped with controllable ultrasonic bath. The DR of 0-33.5 mg/l was achieved under experimental conditions. These results approved that the SF process can be a promising approach in terms of colored wastewater treatment. The data were used for model building by Taguchi and artificial neural network. Further statistical tests were applied to exhibit models goodness and to compare models. Finally, optimization process was carried out using Taguchi and genetic algorithm. The optimization procedure causes optimal point which gives an insight of optimal operating condition.