In this study, nanoparticles of single-phase akaganeite (β-FeOOH) were synthesized by an ultrasound-microwave assisted method. The synthesis parameters were optimized by means of response surface methodology. X-ray diffractions (XRD), Fourier transform infrared spectrum (FTIR), UV-vis diffused reflection spectra (UV-vis DRS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and specific surface area were used to characterize the as-prepared samples. The catalytic activity of the prepared β-FeOOH was evaluated in a heterogeneous photo-Fenton-like process using methyl orange as target pollutant. It is found that the reaction temperature and interaction between microwave and ultrasound have a significant influence on the catalytic properties of the prepared β-FeOOH samples. The β-FeOOH prepared at microwave power of 400 W, ultrasound power of 200 W, reaction temperature of 70°C and reaction time of 3 h, exhibited considerable catalytic activity in weak alkaline solution and under visible light irradiation, which would be of great promise for the industrial application of this catalyst to oxidize organic pollutants for wastewater treatment.