Abstract: Nitric oxide (NO) is a well-known signaling molecular that plays a significant role in stress tolerance of plants to heavy metals. However, the detoxification mechanism of NO has not been well studied. Here, we examined the absorbing and transporting characteristics of copper (Cu) and cadmium (Cd) in tomato seedlings through nutrient solution culture and its response to exogenous NO under Cu and/or Cd stress. Results showed that Cu and Cd with the concentration of 50 μmol·L^-1 greatly inhibited plant growth, with Cd having a higher inhibiting effect than Cu. Under single or dual stresses of Cu and Cd, their contents in both tomato roots and leaves were significantly increased. However, tomato roots showed preference to essential element Cu with a luxury uptake and strictly against Cd through cell plasma membrane in which the content of Cd was only one tenth of Cu in plants. These metal stresses, especially Cd stress, could be alleviated by application of exogenous NO. Tomato plants detoxify these passively-absorbed elements through similar mechanisms, including chelation with glutathione, phytochelatin or metallothionein, as well as vascular compartmentalization. Exogenous NO could alleviate these stresses through regulating the oxidation-reduction condition of GSH-GSSH, controlling the metabolism of GSH-PCs, as well as promoting the vascular compartmentalization of excessive Cu and Cd. In addition, NO could induce higher expression of chelators, such as MTs, GSH and PCs, in both roots and shoots, which showed additive effects to other responses and might be another important detoxification pathway mediated through NO for the responses of tomato plants to Cu and Cd stresses.