In this paper, orthogonal experiment design method was applied to determine the optimum condition for indium leaching from indium-poor zinc residue in HCl solution. Taking the results of range analysis and the situation of industrial production into consideration, the optimum conditions for conventional leaching are: reaction temperature 70°C, concentration of HCl 6 mol/L, leaching time 1.0 h, and ratio of liquid to solid 8:1. Under the optimum conditions, ultrasonic was used to enhance the leaching process. Compared with the conventional leaching process, this new process can provide better indium recovery, shorter leaching time, and faster leaching rate. The indium extraction of indium-poor zinc residue with ultrasonic treatment is up to 96 %, which is 31.0 % higher than that without ultrasonic treatment. In addition, the normal agitation improves the diffusion of solution in the ultrasonically enhanced leaching experiment.