Grinding plays an important role in mining, construction, metallurgy, chemical, coal and other basic industries. In terms of beneficiation, grinding is the most energy consuming operation. So, reasonable grinding conditions according to the properties of ores is the key to obtain good grinding results and reduce energy consumption and resource waste. In this paper, Tongkeng and Gaofeng polymetallic complex ores are taken as research objects, and the effects of grinding law based on single factor condition test and the grinding parameters optimization based on response surface method were studied for two kinds of ores. The results show that grinding time is a significant factor affecting the particle size composition. The suitable grinding concentration of Tongkeng ore and Gaofeng ore is 70% and 75%, respectively. The effect of mill filling ratio on Gaofeng ore is not obvious. The rotational rate has little effect on the grinding technical efficiency. The regression model equations obtained by response surface method are extremely significant, and the relative errors of prediction are all within 1%, indicating high reliability of fitting equations. The order of influencing factors of the two ores is as follows: grinding time > filling ratio > grinding concentration. For Tongkeng ore, the optimized grinding conditions are grinding time 5.4 min, grinding concentration 67% and filling ratio 35%. For Gaofeng ore, the optimized grinding conditions are grinding time 3.8 min, grinding concentration 73% and filling ratio 34%.