The effect of lizardite on talc flotation when using carboxymethyl cellulose (CMC) as a depressant was studied by micro-flotation experiments and adsorption measurements, zeta-potential measurements, magnesium ion dissolution analysis, and solution chemistry calculation. The results for the micro-flotation experiments showed that the addition of lizardite further decreased the floatability of talc at pH 8.5 when using CMC as the depressant. The mechanism was that magnesium ions dissolved from lizardite lattice, then formed hydrolyzed species of magnesium cations and interacted with talc surfaces, which promoted CMC adsorption, and thus decreasing talc floatability.