Both vertical mills and ball mills are large grinding equipment in industry, which are widely used in mineral processing, metallurgy, chemical engineering, coal, and other fields. The vertical mill and ball mill were used for grinding tests to compare the grinding effect on certain lead-zinc ore, meanwhile sieve analysis, monomer dissociation analysis and froth flotation tests on above products were also conducted. The results of sieve analysis and monomer dissociation analysis showed that the content of coarse fraction in the product after vertical mill grinding decreased by 0.6 percentage compared with the test results of ball mill. In addition, the liberation degree of galena and sphalerite increased by 2.28 and 1.60 percentage respectively. The froth flotation tests demonstrated that compared with the ball mill-flotation test results, the grade and cumulative recovery of lead in the lead concentrate increased by 0.65 and 0.61 respectively, and the grade and cumulative recovery of zinc in the zinc concentrate increased by 0.6 and 0.6 respectively. The lead and zinc content in the sulfur concentrate decreased by 0.02 and 0.06 percentage. In summary, the grinding effect of the vertical mill for this lead-zinc ore is better than that of the ball mill.