Abstract: With the implementation of carbon peak and carbon neutrality vision, an amine collector has been extensively applied in reverse flotation of bauxite, iron, and phosphate ores for desiliconization. Previous research indicates that the molecular structure of flotation reagents has a significant influence on their collecting performance and flotation selectivity. Regarding the substituent effect of organics, a method wherein a suitable substituent is inserted into existing reagents has been used to develop new high-performance flotation reagents. To clarify the effect of methyl on collection ability and flotation selectivity of cationic collectors, flotation separation of quartz and hematite has been conducted. C12 alkyl cationic surfactants such as dodecyl amine, dodecyl methylamine, N,N—dimethyl dodecyl amine, and dodecyl trimethyl ammonium chloride were selected as collectors. The active mechanism of methyl on the flotation performance of cationic collectors was also determined by calculating the electrostatic potential of the collectors and the van der Waals volume of its polar group. The collection abilities of cationic collectors were investigated by single mineral flotation. The results indicate that flotation recoveries of quartz and hematite are decreased with the insertion of a methyl group into central atom of a cationic collector. Further, the effect of methyl on selectivity of cationic collectors was investigated by flotation separation of artificially mixed quartz and hematite. The results revealed that the separation efficiency of artificially mixed quartz/hematite is increased gradually due to the drastic reduction in hematite flotation recovery rate. A methyl group is an electron donating group. The calculation and diagramming of electrostatic potential for selected collectors reveal that the charge distribution density of the cationic collector is varied by the introduction of an electron donating group. Consequently, the charge number of central atom is increased, thereby weakening the positive electrostatic potential of the atom and making the electrostatic adsorption strength between collector and mineral surface lower. Therefore, the flotation recovery rate decreased. Meanwhile, the size of a polar group for cationic collectors is enlarged by introducing the methyl group, thus increasing the steric hindrance of reagents and mineral surface interaction and resulting in an increase in flotation selectivity. With an increase in the methyl group number, the flotation separation efficiency of artificially mixed quartz and hematite becomes increasingly high. In the future, obtaining and quantifying correlation parameters of substituents and then explicating the relationship between substituent parameters and flotation performance of cationic collectors would be beneficial to establish a new design method for cationic collectors.