In this study, the flotation behavior of malachite was investigated using hydrophobic talc nanoparticles (TNs) as collectors. To improve the floatability of TN-deposited malachite, various experimental parameters were systematically investigated. We found that the floatability sharply increased as the size of the TNs decreased. The floatability of malachite was enhanced in the presence of smaller TNs, since higher amounts of smaller TNs were deposited on the surface of the malachite, thus rendering the surface more hydrophobic. Moreover, the floatability of the TN-deposited malachite increased as the pH decreased, likely due to the more favorable interaction between TNs and malachite by means of electrostatic attraction. Furthermore, the floatability became more enhanced as the TN concentration increased, likely associated with increases in the amount of TNs deposited on the surface of the malachite, thus enhancing the floatability by altering the hydrophobicity of the surface. Our findings suggest that the application of natural hydrophobic TNs as collectors in malachite flotation should be introduced as a new concept.