An industrial experiment was carried out to study the characteristics and formation mechanism of segregation in semi-continuous direct-chill (DC) casting of Φ300mm aluminum alloy billet with ultrasonic radiation of different powers. Results show that both microsegregation and macrosegregation of solute elements Zn, Mg, Cu are improved remarkably when ultrasonic vibration is applied to A1-Zn-Mg-Cu alloy. Meanwhile, the higher power of ultrasonic vibration is, the more homogeneous distribution of solute elements becomes, and then the more effective improvement of segregation is achieved. With a 240W ultrasonic treatment (UST), the intra-grain solution degree of elements Zn, Mg and Cu increases by 35.8%, 41.8% and 40.2% respectively while the macrosegregation ratio decreases by 10.3%, 7.4%, 6.7%. Physical and chemical effects caused by ultrasonic field exert a positive impact on the solute elements diffusion, grain refinement, the depth of sump and solution degree et al, which contribute to the improvements of segregation.