Abstract: In order to study the crystal structure of pyrite and the molecular configuration of butyl pyrite from the perspective of computational chemistry, and to investigate the interaction between flotation chemicals and pyrite, this paper investigated the energy band structure, density of states and charge density of pyrite crystals through density functional theory, and carried out quantum chemical calculations on butyl pyrite molecules, analyzed the energy of its front orbitals and the distribution of electron density, and finally calculated the interaction energy of a single agent, collector butyl xanthate, and activator copper sulfate with the surface of pyrite, and the change rule of interaction energy when they act together. Finally, the interaction energies of the single−agent collector butyl xanthate and activator copper sulfate with the pyrite surface and the change rule of the interaction energy of the system when they act together were calculated by molecular dynamics method. The results show that pyrite is a direct bandgap semiconductor with a forbidden bandwidth of 0.672 eV. The negative charge of the butyl pyrite molecule is mainly concentrated around the sulfur atom, and its highest occupied molecular orbitals are mainly contributed by the orbitals of the sulfur atoms, which are the main active sites. When the agent molecules interact with the pyrite surface, the total energy of the system shows a decreasing trend, and the absolute value of the interaction energy is as follows: butyl xanthate+copper sulfate > butyl xanthate > copper sulfate. That is, the interaction energy in the system of butyl xanthan and copper sulfate decreases the most, at this time, the agent and pyrite surface adsorption is strong, enhancing the hydrophobicity of the pyrite surface, which is conducive to the recovery of pyrite flotation.