Based on the flotation test of copper zinc sulfide ore, the effect of sodium hexametaphosphate on chalcopyrite and sphalerite was investigated by combining microcalorimetry and adsorption amount test, aiming to explain the inhibition mechanism of sodium hexametaphosphate from the perspective of thermodynamics and provide a basis for the efficient flotation separation of copper zinc sulfide ore. The results showed that the concentration of 2X 10-4 mol/L sodium hexametaphosphate at pH = 9 had a good separation effect on chalcopyrite and Cu2+ activated sphalerite,and the flotation recovery of Cu2+ activated sphalerite was reduced from 85.13% to 28. 51 %, and the recovery of chalcopyrite was reduced from 95. 15% to 90. 77%. Before the action of sodium hexametaphosphate, the apparent activation energy Ea of sodium diethyldi thiocarbamate with chalcopyrite and Cu2+ activated sphalerite were 36. 95 kJ/mol and 57. 28 kJ/mol, respectively; after the action of sodium hexametaphosphate, the apparent activation energy Ea of sodium diethyldi thiocarbamate adsorbed on the surface of chalcopyrite and Cu2+ activated sphalerite increased by 13. 07% and 37. 08%,respectively? which increased the apparent activation energy of sodium diethyldi thiocarbamate on the surface of Cu2+ activated sphalerite and Cu2+ activated sphalerite. The adsorption difficulty of ethionite on Cu2+ activated sphalerite surface was increased by 13. 07% and 37. 08%, respectively, which increased the difficulty of ethionite adsorption on Cu2+ activated sphalerite surface, while it had less effect on ethionite adsorption on chalcopyrite surface.