Response surface methodology is used to optimize the leaching process for refractory flotation copper tailings. The proportion of the refractory combination oxide copper (chrysocolla) is 64.84%. At present, few studies have examined the leaching of chrysocolla. In this study, we examine the effects of several variables, including the amount of concentrated sulfuric acid, leaching temperature, and leaching time, on leaching efficiency. Using a response surface methodology, we develop a quadratic model relanbting all the above experimental variables with leaching efficiency. The resulting model is highly consistent with experimental data. According to the model, the factor with the greatest influence on leaching efficiency is the amount of concentrated sulfuric acid. According to the model, the optimal leaching conditions are 85 kg/t concentrated sulfuric acid, a leaching temperature of 68.51 °C, and a leaching time of 4.36 h. The actual measured leaching efficiency under these conditions is 85.86%, which is close to the value of 86.79% predicted by the model. We study the leaching processes using scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) surface scan analyses. Both methods allow us to explore the content of the main element and visually observe its distribution, allowing us to develop effective methods for treating low-grade oxide ores.