Silicon (Si) and Zinc (Zn) have been frequently used to alleviate cadmium (Cd) toxicity, which are feasible strategies for crop safety production. However, the mechanisms underlying the interaction of Si and Zn on alleviating Cd toxicity are not well understood. A hydroponic system was adopted to evaluate morphological, physiological-biochemical responses, and related gene expression of wheat seedlings to Si (1 mM) and Zn (50 µM) addition under Cd stress (10 µM). Cd induced obvious inhibition of wheat growth by disturbing photosynthesis and chlorophyll synthesis, provoking generation of reactive oxygen species (ROS) and interfering ion homeostasis. Cd concentration was decreased by 68.3%, 43.1% and 73.3% in shoot, and 78.9%, 44.1% and 85.8% in root by Si, Zn, and combination of Si with Zn, relative to Cd only, respectively. Si and Zn effectively ameliorated Cd toxicity and enhanced wheat growth; but single Si or combination of Si with Zn had more efficient ability on alleviating Cd stress than only Zn, indicating Si and Zn have synergistic effect on Cd toxicity; Interaction of them alleviated oxidative stress by reducing ROS content, improving AsA-GSH cycle and antioxidant enzymes activities, and regulating Cd into vacuole through PC-Cd complexes transported by HMA3 transporter. Our results suggest that fertilizers including Si and Zn should be made to reduce Cd content, which will beneficial for food production and safety.