An original ultrasound (US) directly intensified photocatalytic reactor was designed to degrade azo dye pollutant methyl orange (MeO) using Degussa TiO2 as the photocatalyst. The sonolytic, photocatalytic and sonophotocatalytic degradation of MeO in the new reactor and the synergistic effect between sonolysis and photocatalysis were investigated. Effects of operation parameters i.e., US power, TiO2 dosage, liquid circulation velocity and air flow rate on degradation efficiency were investigated and optimized. The results showed that all parameters have optimal values for the sonophotocatalytic degradation of MeO, and the optimum conditions for the new process are US power 600W, TiO2 dosage 3g/L, liquid circulation velocity 4.05×10−2m/s and air flow rate 0.2L/min. Under the optimum conditions, 91.52% MeO had been degraded within 1h, and the combination of sonolysis and TiO2 photocatalysis exhibited an obvious synergetic effect.