Abstract: The influence mechanism of polyacrylamide (PAM) residue on the flotation of low rank coal during coal slurry water treatment is investigated using low rank coal from the Panji and Pan Yidong Coal Processing Plants in the Huainan Mining Area. A model of the characteristic structural unit of low rank coal is constructed using X-ray diffraction and infrared spectroscopy. Density Functional Theory (DFT) calculations are employed to study the adsorption interactions between water molecules, dodecane, PAM adsorption structural units, and the characteristic structural units of low rank coal. The DFT results are validated through flotation tests conducted with varying PAM dosages to assess the impact of PAM residue on flotation performance. The DFT results indicate that the average adsorption energies of water molecules, dodecane, and PAM adsorption units with the characteristic structural units of low rank coal are −0.35, −0.39, and −0.50 eV, respectively. The adsorption stability follows the order: polyacrylamide (PAM) > dodecane > water molecules. This indicates that in the competitive adsorption system, PAM has formed a more stable adsorption configuration on the surface of low-rank coal, rendering it difficult for dodecane to effectively displace the pre-adsorbed PAM molecules. Among the three PAM adsorption structural units, P−DAC shows the strongest adsorption with the low rank coal characteristic structural unit, significantly reducing both the adsorption sites and capacity of dodecane. This results in decreased overall adsorption stability in the competitive adsorption system, weakening the trapping effect of dodecane. The adsorption mechanism between low rank coal characteristic units and water molecules is mainly governed by hydrogen bonding and van der Waals force, with hydrogen bonding being the dominant driving force. In contrast, the adsorption of low rank coal units with dodecane and PAM is primarily driven by van der Waals force, with P−AM and P−AA assisting adsorption through hydrogen bonding with −C=O groups. PAM molecules influence the charge transfer between collecting agents and low rank coal units, further weakening the adsorption effect and reducing adsorption stability. Flotation tests reveal that while PAM enhances fine coal yield, it significantly increases the ash content of fine coal, reduces flotation recovery and performance indices, leading to an overall deterioration in flotation efficiency. The combined DFT and experimental findings suggest that the polar groups in PAM have low selectivity, causing both coal and gangue minerals to be floated simultaneously. Furthermore, the flocculation effect of PAM interferes with the effective adsorption of collecting agents and hinders the hydrophobicization of coal particles, further compromising flotation performance. This study provides a theoretical basis for optimizing flotation processes and the rational use of flocculants through DFT simulations and flotation tests.