Abstract: The collision probability between fine copper oxide particles and bubbles is low, it is difficult to recover them effectively by sulfurization flotation.In this paper, sulfuric acid leaching test is carried out on a fine refractory copper oxide whose main gangue is silicate mineral.In order to obtain the best condition and the best leaching rate, RSM is used to optimize the process.Firstly, the Box-Behnken module in Design expert 10.0 is used to design the experimental scheme, and the quadratic regression equation model is established according to the experimental data, and the variance analysis is carried out.According to the contour line and the response curve, the interaction between the factors on the copper leaching rate is analyzed.Using design expert 10.0 software to optimize the analysis, get the optimal parameters of the leaching test and carry out the verification test.The optimal experimental conditions are as follows sulfuric acid concentration is 175 g/L, liquid-solid ratio is 3.5, leaching time is 120 min.Under this condition, the validation test is carried out, and the ideal index of copper leaching rate is 88.43%.The model has high reliability and the test design is reasonable.This optimization process can be used as a reference in production.