Heavy metals such as Cu and Cd are important pollutants. Quillay (Quillaja saponaria) is a tree species endemic to Chile that is of worldwide commercial interest due to its saponins. It can grow on contaminated sites. However, the biological mechanisms underlying its defensive responses remain elusive. This study aimed to characterize Quillay plants under Cu and Cd stress and identify mechanisms controlling their interaction with these metals. We subjected six-month-old plants to Cu (75, 150, and 300 mu M) and Cd (20, 40, and 80 mu M) in hydroponics for a week and assessed growth, metal accumulation, saponin production, and the expression of a suite of stress-induced genes. Those genes are related to phytochelatins (PCS) and metallothioneins (MT), the antioxidant system (GS and GR), and metal transporters (COPT1). The results indicated that both metals were accumulated mainly in roots, with 339.9 and 433.8 mg/kg DW, for Cd and Cu, respectively, exhibiting a metal excluder pattern. Cd increased the length of the principal root. Higher doses of Cd and Cu augmented the saponin content (62.8% and 41.2% compared to control, respectively). The genes GS, GR, and COPT1 modified their transcriptional levels depending on the metal and organ evaluated. These results provide evidence of specific defensive responses of this species against heavy metal stress, which is helpful to guide new research efforts and support the development of strategies for using Quillay for phytoremediation.