Abstract: This is an article in the field of mineral processing engineering. For the flotation of sulfide ores whose gangue mineral is serpentine, serpentine can deteriorate the flotation of sulfide ores due to its easy mudification. To solve this problem, 2-hydroxyphosphonoacetic acid (HPAA) was used for the first time in this paper to eliminate the negative effect of serpentine on chalcopyrite flotation. In this article, the effect of HPAA on chalcopyrite/serpentine flotation system and the mechanism of action were investigated by microflotation test, turbidity test, zeta potential test, adsorption amount test and XPS test. The tests showed that serpentine is positively charged and chalcopyrite is negatively charged. Due to the electrostatic attraction, serpentine slime will adsorb on the surface of chalcopyrite, thus inhibiting the flotation of chalcopyrite. After adding HPAA, the flotation recovery of chalcopyrite was increased from 47.85% to 92.44%. The mechanism was that HPAA chemisorbed with Mg²⁺ of serpentine, which significantly reduced the surface potential of serpentine and caused repulsive effect on mineral particles, thus recovering the floatability of chalcopyrite.