Cadmium (Cd) contamination in agricultural soil is a worldwide environmental problem. In situ stabilization has been considered an effective approach for the remediation of Cd-contaminated agricultural soil. However, information about the long-term effects of amendment on soil properties and stabilization efficiency remains limited. In the present study, mercapto-functionalized nano-silica (MPTS/nano-silica) was used to stabilize Cd in contaminated agricultural soil under field conditions for three years (with application rates of 0%, 0.2%, 0.4%, 0.6%, 0.8% and 1.0%). The application of MPTS/nano-silica reduced the soil aggregate stability (PDA(0.25)) (14.8%) and available K (24.9%) and significantly increased the soil dehydrogenase (DHA) (43.4%), yield of wheat grains (33.5%) and Si content in wheat tissues (55.2% in leaf, 50.4% in stem, and 37.7% in husk) (p < 0.05). More importantly, MPTS/nano-silica decreased the leachability (36.0%) and bioavailability (54.3%) of Cd in the soil and transformed Cd into a more stable fraction. The content of Cd in wheat grains decreased by 53.9%, 61.9% and 54.1% in 2017, 2018 and 2019, respectively, in comparison with the control. These results indicated that MPTS/nano-silica has long-term stabilization effects on Cd in agricultural soil and is a potential amendment for the remediation of Cd-contaminated agricultural soils.