Flotation separation of pyrite from high-sulfur bauxite remains challenging because of its high clay mineral content. To investigate the influence mechanisms of major clay minerals on pyrite flotation in high-sulfur bauxite, flotation tests were conducted under various conditions. Mineral liberation analysis revealed that kaolinite and illite collectively constitute ~95% of the clay minerals in a Henan high-sulfur bauxite ore. Flotation tests demonstrated their differential effects under acidic/alkaline conditions: In acidic pulp with 1×10^-3 mol/L sodium butyl xanthate (SBX), the actual recovery (ε_a) of kaolinite/illite-pyrite pulp was 10% lower than the theoretical recovery (ε_T). Conversely, under alkaline conditions, ε_a exceeded ε_T by 15-20%. Analysis showed that under acidic conditions, opposite surface charges between kaolinite/illite and pyrite caused electrostatic adsorption, occupying SBX adsorption sites on pyrite. This reduced pyrite’s surface hydrophobicity and hindered hydrophobic agglomeration. Additionally, fine kaolinite/illite particles coated pyrite surfaces, blocking SBX adsorption and weakening collection efficiency. Under alkaline conditions, dissolved substances from kaolinite/illite inhibited hydrophilic substance formation on pyrite surfaces, freeing more SBX adsorption sites. Furthermore, some kaolinite/illite particles adsorbed onto pyrite surfaces and floated as "carriers" with pyrite, resulting in higher ε_a than ε_T in alkaline environments.