Abstract: Vicia faba seedlings were hydroponically cultivated in different concentrations of carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) (0, 2.5, 5.0, and 10 mg·L^-1), 20.0 μmol·L^-1 Pb+5.0 μmol·L^-1 Cd (shortened as Pb+Cd), and Pb+Cd+MWCNTs-COOH for 15 days respectively, and several related physiological and biochemical parameters were assayed to evaluate the ecotoxicological risks of MWCNTs-COOH and its joint exposure with Pb+Cd in the leaves. The results show that the reactive oxygen species (ROS) such as superoxide radical (O₂^·-) and hydrogen peroxide (H₂O₂) were overproduced in response to MWCNTs-COOH exposure or combination with Pb+Cd compared with the control, accompanied by enhanced patterns of isozymes and total activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and guaiacol peroxidase (POD). The activities of CAT were activated significantly under 2.5 mg·L^-1 of MWCNTs-COOH or combined with Pb+Cd, however, it decreased significantly under 10.0 mg·L^-1 Pb+Cd+MWCNTs-COOH. Thus, CAT activities can be used as a sensitive biomarker for early warning of MWCNTs-COOH exposure or combination with heavy metals in the contaminated environment. MWCNTs-COOH exposure resulted in the accumulation of carbonylated proteins, heat shock protein 70 (HSP70), and non-protein thiol (NPT), as well as activated the activities of endopeptidase (EP) isozymes enhancing. After combination with Pb+Cd, the production of carbonylated proteins and NPT, and the activities of EP isozymes were significantly enhanced, whereas HSP70 presented in a declined state, The increased activities of antioxidant enzymes and EPs, and the overproduction of HSP70 and NPT should be the crucial defense mechanisms in the Vicia faba seedlings to alleviate the oxidative stress and damage under MWCNTs-COOH exposure or combined with Pb+Cd. It can be concluded that MWCNTs-COOH caused oxidative stress and defense responses in the leaves of Vicia faba seedlings, and the joint exposure with Pb+Cd aggravated the oxidative damages and protein degradation.