Abstract: Quartz is one of the main gangue minerals in silica−calcareous collophanite. In the reverse flotation desilication process, the poor selectivity of the common dodecylamine (DDA) collector leads to low flotation separation efficiency. The combination of dodecylamine and nonionic surfactant isomerol polyether (XL−40) was adopted to investigate the feasibility of reverse flotation separation of quartz and apatite in this study. The interaction mechanism of mixed collector was accomplished through the measurements of foam stability, contact angle, adsorption and Zeta potential. The single−mineral flotation tests showed that DDA has good floatability for both minerals under neutral pH conditions. However, when the dosage of DDA was 6 mg/L, the addition of XL−40 promoted the flotation of quartz while reduced the floatability of apatite, illustrating that DDA and XL−40 mixture had a selectively between quartz and apatite compared to DDA. The results of the artificial mixed minerals flotation test showed that the grade and recovery of P₂O₅ were 27.12% and 84.87% respectively in the concentrate with the addition of the individual DDA collector, while the grade and recovery of P₂O₅ were 32.86% and 85.88% respectively in the concentrate when using DDA and XL−40 mixture as the collector. The interaction mechanism analysis demonstrates that the DDA and XL−40 mixture significantly improves the fluidity of both two−phase and quartz three−phase foams. The mixed DDA and XL−40 exhibited strong co−adsorption on quartz surfaces while weakly adsorbed adsorption on apatite surfaces. Contact angle measurements reveal that the quartz surface contact angle reaches approximately 85°, whereas the apatite surface contact angle is only 30° in the presence of DDA and XL−40 mixture. This substantial difference in hydrophobicity/hydrophilicity between the two minerals, then achieving the separation of two minerals. This study provides a reference for the assembly of cationic collector and nonionic surfactant for the reverse flotation removal of quartz in the phosphate ore flotation system.