Effective removal of toxic mercury(II) from aqueous media is a primary challenge for public health and environmental protection. In this work, dendritic mesoporous silica nanoparticles modified with thiol moieties (denoted as TDMSNs) are used as nanoadsorbents to trap mercury(II) ions. It is demonstrated that the exceptionally high density and accessibility of thiol moieties are both necessary to achieve efficient mercury(II) decontamination. TDMSNs with the highest surface thiol group density of 283.2 μmol g⁻¹ exhibit a Hg(II) adsorption capacity of 1502.4 mg g⁻¹, outperforming reported thiolated adsorbents. The large and well-exposed mesopores of TDMSNs enable fast adsorption kinetics within 5 min to reduce the mercury(II) concentration from 10 ppm to below 2 ppb (US Environmental Protection Agency acceptable limit) which is faster than those in previous reports. Furthermore, the TDMSNs show adsorption stability in a wide range of pH and promising reusability performance (89% adsorption capacity maintenance after 5 reuses). Our contribution paves the way for the rational design of nanoadsorbents for efficient environmental pollutant remediation.