The work aims to prepare optimum slurry for ultrasound fine atomization chemical mechanical polishing (CMP) of zinc selenide. With alumina abrasive, pH value regulator tetramethyl ammonium hydroxide, oxidant hydrogen peroxide and surfactant polyvinylpyrrolidone as main active ingredients, fine atomization CMP of ZnSe was carried out, and removal mechanism was analyzed through orthogonal experiment by taking material removal rate (MRR) and surface roughness (Ra) as assessment indicators. Then the experimental results were compared with those of traditional polishing. Provided that mass fraction of alumina was 9%, pH value was 11, hydrogen peroxide was 3.5% and polyvinylpyrrolidone content was 0.75%, the material removal rate was up to 923.67 nm/min and surface roughness was merely 2.13 nm. Under the same working conditions, the material removal rate and surface roughness of traditional polishing material was 965.53 nm/min and 2.27 nm, respectively. Among all constituents of the polishing slurry, alumina abrasive has the most influence on test results, followed by oxidant, pH value and surfactant. The effect of fine atomization polishing is similar to that of traditional polishing, but the consumed quantity of polishing slurry is only 1/8 of the latter.