Phytoremediation is commonly used to remediate copper (Cu) pollution in water bodies. Epipremnum aureum is often used as a restoration plant because of its rapid reproduction, high population density and high landscape value. However, neither its ability to remediate Cu-polluted water nor its mechanism of resistance to Cu stress has been fully clarified. Therefore, the present study revealed the Cu removal ability and resistance mechanism of E. aureum through physiology and metabolomics. And based on the results of this study, the response surface was applied to the application of plant growth regulator (PGR) to propose a precise restoration program. We first examined the growth physiological indices and repair of Cu in E. aureum under different Cu stress levels and found that the resistance mechanism of E. aureum to Cu was significantly initiated at 400 mg·L-1. And as the level of Cu stress increased, the Cu content in the plant also increased, and the underground part was the main accumulating part. The translocation factor of E. aureum was <1, and the bioconcentration factor was greater than 1 at all different Cu concentrations. Subsequently, metabolomics studies on E. aureum concluded that arginine and proline metabolism, indole alkaloid synthesis and brassinosteroid biosynthesis are the major pathways involved in the mechanism of Cu stress resistance in E. aureum. Based on these results, we proposed that salicylic acid, sodium nitroprusside and 2,4-epibrassinolide could be selected as PGRs, and further optimized the administration of PGRs using response surfaces. The optimized scheme allowed E. aureum to reach a maximum Cu removal of 84.39 % under 400 mg·L-1 Cu stress, which was 35.61 % higher than the non-fortified treatment. This study provides supporting materials and application options for the Cu repair capacity and resistance mechanisms of E. aureum.