The interaction between chalcopyrite and illite particles was analysed using ζ-potential measurements and flotation tests. Statistically designed tests were used to examine the factors controlling flotation (frother concentration, dispersant concentration, froth height, airflow rate and amount of clay). Furthermore, the significance levels of the impacts of these factors on responses (chalcopyrite grade/recovery, pyrite grade/recovery, dynamic froth stability and mean bubble diameter) were determined. Chalcopyrite and pyrite ζ-potentials were measured in the presence of illite. The addition of 15% illite to the chalcopyrite, especially between pH 11 and 12, shifted the ζ-potential values closer to that of pure illite, indicating complete surface coating of chalcopyrite with illite. In the flotation experiments, better results were obtained in terms of chalcopyrite grade at a low airflow rate and a high froth height. With increasing froth height there was a decline in the gangue mineral recovery as the residence time of the froth increased. The most significant factor increasing pyrite recovery was the amount of clay. Although illite is considered to be the least problematic clay mineral for flotation, as reported in the literature, an illite content of as low as 5% in the ore decreased chalcopyrite grade by 3.83%. While K and Na contents of 4% were detected after flotation without the addition of illite, their abundance increased to 5.7% after the addition of illite.