It was well documented that a mixture of collectors could have synergistic advantages over the use of an individual collector for apatite flotation. Therefore, it would be an essential procedure to determine an optimum amount of each collector for development of an efficient mixture (collector). In this study, a mixture design (MD) model was used to find an optimum amount of different typical apatite anionic collectors (Atrac, Alke and Dirol) and make an efficient mixture for the direct flotation of a low grade apatite ore. Assessment of responses for apatite flotation tests which their collectors were designed by MD showed that Dirol has the highest selectivity whereas Alke has the highest collectivity for the direct flotation of apatite. According to the experiments, the MD model computed that a mixture collector with Dirol: 364 (g/t), Alke: 295.2 (g/t) and Atrac: 140.8 (g/t) concentrations can provide the most efficient responses through the apatite flotation. Results based on the purposed concentrations for the mixed collector demonstrated that higher apatite flotation responses (grade: 14%, recovery: 76%, and S.E.: 66%) in comparison with the performance of tests with a single collector. These results can be used to design flotation conditions for the apatite flotation-separation in the industrial scale and assessment of collector concentrations for other investigations.