Oxidative acidification of high-sulfur bauxite can cause great problems in the production of alumina by the Bayer process. In this study, sodium hydroxide was used as a hot alkali solution to pretreat high-sulfur bauxite by hot alkali milling, which inhibited the effect of oxidative acidification on flotation, and then flotation treatment was carried out, to improve the grade of alumina and reduce the sulfur content of high-sulfur bauxite, and finally meet the production requirements of Bayer alumina. The results showed that under the optimal conditions of sodium hydroxide solution concentration of 40%, temperature of 60°C, and grinding time of 4 minutes, the alumina grade increased from 57.18% to 87.45% and the sulfur grade decreased from 5.46% to 0.69% by pretreated flotation. XRD, SEM, EDS, and AFM were used to analyze the pretreatment mechanism of the hot alkali mill, and it showed that the pretreatment of the hot alkali mill would corrode the surface of diaspore monohydrate and expose more surface sites. The hot alkali solution pretreatment restrained the acidification and oxidation of pyrite. The hot alkali solution pretreatment makes the surface of pyrite rougher and enhances the floatability of pyrite.