Existing collectors used in the flotation process of bastnaesite ores are characterized by the poor flotation performance and low recovery. In this paper, from the perspective of molecular structure, ethyl O-mesitylsulfonylacetohydroxamate (C₁) was selected as a novel collector for bastnaesite ores, and compared with the most commonly used collector, salicylhydroxamic acid (C₂), in the flotation test with bastnaesite ore with fine mineral particles, complex embedding and a high mud content. The flotation test confirmed that C₁ had the better collection ability and flotation performance than C₂. Then, the adsorption mechanisms between collectors (C₁ and C₂) and bastnaesite surface were explored based on first principles thinking. The adsorption energies between collectors (C₁ and C₂) and the (110) plane of bastnaesite were respectively calculated as -1.79 eV and -1.44 eV and corresponding adsorption heights were respectively 1.65 Å and 2.43 Å. These data indicated that C₁ had the better affinity to the (110) plane of bastnaesite and the better binding. The calculation results of partial density of states (PDOS) showed that both collectors underwent significant orbital hybridization with the (110) plane of bastnaesite, suggesting strong electronic interactions.