Utilizing the ultrasonic pretreatment, flotation tests, ICP-OES, and XPS analysis, the effect of the different ultrasonic pretreatment methods on the flotation behavior of galena were investigated. The flotation recovery of galena was improved for pretreated single galena sample, which is mainly attributed to the efficient removal of the oxidized components and contaminants on the surface of galena by the acoustic cavitation. However, the flotation recovery of galena was decreased when pretreated mixture sample of galena and pyrite was used. Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) and X-ray photoelectron spectroscopy (XPS) results reveal that ultrasonic pretreatment facilitates the conversion of PbS to Pb(OH)2 and PbSO4. Besides, the flotation recovery of galena was affected to varying degrees when the galena was mixed with the pyrite of the different particle sizes in the ultrasonic pretreatment process. The reason is that the change in the surface area ratio of these two minerals affects the electrochemical reaction rate between galena and pyrite.