The properties and flotation behavior of coal-pyrite were analyzed by the contact angle, induction time, and flotation tests. The results indicate that compared with coal, coal-pyrite has a smaller contact angle and longer induction time. The floatability of coal-pyrite is poor with dodecane as the collector. A part of fine liberated pyrite mixed with the clean coal in flotation. The linear relationship between the ash and liberated pyritic sulfur recoveries implies the same recovery mechanism, that is, mechanical entrainment. Molecular dynamics simulation also demonstrates that dodecane could not break through the hydrated film to be absorbed on the pyrite surface.