Pressure leaching of indium-bearing zinc oxide dust in sulfuric acid medium was studied by orthogonal experiments and single-factor experiments. The results showed that the important degree of various factors affecting the leaching rates of In followed the order of initial acidity > ratio of liquid to solid > pressure > temperature > time, and that affecting the leaching rate of zinc was the initial acidity > ratio of liquid to solid > temperature > time > pressure. The optimum conditions were obtained as the leaching temperature of 140℃, pressure 0.6 MPa, reaction time 90 min, ratio of liquid to solid 8 mL/g, initial acidity of 160 g/L, and stirring speed 500 r/min. Under the optimum conditions, the leaching rates of zinc and indium were over 99% and 91%, respectively, zinc and indium could be efficiently leached out with low content residual acid and good process stability.