Design of new adsorbents for complete removal of thallium(I) from wastewater is of significant importance. Based on the theory of binding ability between crown ether and metal ion, a kind of Tl(I)-selected crown ether, thio-18-crown-6 ether, was designed. Subsequently, modeling calculations were performed to investigate the microscopic interaction between 18-crown-6 ether and its sulfur-substituted derivatives with Tl⁺. The results showed that thio-18-crown-6 ether generally showed higher affinity to Tl⁺ than 18-crown-6. The stabilities of these complexes ranked in an order of 5S-18C6 > 4S-18C6(II) > 2S-18C6(I) > 2S-18C6(II) > 6S-18C6 > 3S-18C6 > 18C6 > 1S-18C6. The binding energies of 5S-18C6 with free Zn²⁺, Pb²⁺, Cu²⁺, and Cd²⁺, which are usually impurity ions in thallium-containing wastewater, were more negative than with Tl⁺, indicating more affinity of 5S-18C6 toward these free two-valence ions. However, after the influence of solvent (water) was taken into account, 5S-18C6 showed fairly high selectivity to Tl(I) over Zn²⁺, Pb²⁺, Cu²⁺, and Cd²⁺. Therefore, 5S-18C6 should be a proper compound which has the promising potential to be adopted for the complete and selective removal of Tl(I) from wastewater. Further synthesis and adsorption experiments are needed to verify this prediction.