Cadmium (Cd 2+ ) is a toxic heavy metal impairing plant growth and development. Xyloglucan endotransglucosylase/hydrolase gene (XTH) is involved in the plant response to heavy metal toxicity, in addition to controlling cell wall extensibility. However, the link between XTH and Cd 2+ stress has not yet been established in higher plants. PeXTH expression was up-regulated by 1.2–2.1-fold in Populus euphratica roots and leaves upon Cd 2+ exposure (40–80μM CdCl 2 ). Cellular Cd 2+ analysis and flux data showed that the cadmium-elicited expression of PeXTH markedly restricted Cd 2+ uptake and accumulation in P. euphratica roots. Moreover, tobacco plants overexpressing PeXTH were more tolerant to Cd 2+ stress (80μM CdCl 2 ) than wild-type tobacco in terms of root and shoot growth. Transgenic lines accumulated 49–58% less Cd 2+ in root apical and mature regions, as compared to the wild type. The less buildup of Cd 2+ in roots of transgenic lines was the result of lower influx of Cd 2+ under Cd 2+ stress. It is noting that transgenic plants displayed 56–87% higher xyloglucan degradation activity (XDA) than the wild type, leading to a 25–27% decline of xyloglucan content in the root cell walls. Therefore, overexpression of PeXTH increased the activity of XDA in transgenic plants, which enhanced the degradation of xyloglucan in the wall. The down-regulated amount of xyloglucan led to less binding sites for Cd 2+ and thus reduced the root Cd 2+ uptake and buildup in transgenic plants. Consequently, the Cd 2+ toxicity was eventually alleviated in transgenic tobacco.