Abstract: This study attempts to address the low separation efficiency of iron ore in Hebei Province. We conducted a single factor test based on the properties of iron ore to investigate the effects of ball mill medium filling rate, material-ball ratio and rotation rate on the grade and recovery rate of iron concentrate in grinding products. Then, based on this single factor test, we established the response surface model of the grade and recovery rate of iron concentrate by introducing the response surface design so as to reveal the coupling effect between multiple parameters in the grinding process and optimize process parameters. Three-dimensional modeling and decoupling analysis were carried out. Results show the optimum grinding conditions, 42% medium filling rate, 0.064 material-ball ratio and 77.3% rotation rate. Under such conditions, 3 verification tests revealed that the average values of TFe grade and recovery rate were 65.18% and 84.22%, respectively, and the separation efficiency reached 73.24%. Compared with the single factor test, the TFe grade and recovery rate increased by 1.13 percentage points and 2.39 percentage points, respectively, and the separation efficiency increased by 4.59 percentage points.