Based on the coordination chemistry of crown ether and soft and hard acid-base theory (HSAB) of crown ether, five kinds of thiacrown ethers were designed and synthesized. And their complexation abilities to two soft acid ions-Ag(I) and Tl(I) were systematically investigated. Firstly, the five crown ethers and their complexes with Ag(I) and Tl(I) complexes were optimized by Gaussian 16 software. On this basis, the Gibbs free energy change (ΔG), enthalpy change (ΔH), internal energy change (ΔU) and other thermodynamic parameters of the complexation process of five sulfur crown ethers with Ag(I) and Tl(I) at 298.15 K were calculated. The simulation results showed that the five thiacrown ethers had changed after being complexed with Ag(I) and Tl(I), and the ΔG and ΔU of the five crown ethers after structural optimization were negative in the complexation process with Ag(I), showing a certain coordination ability. However, during the complexation with Tl(I), ΔG and ΔU were close to 0, and the coordination ability was relatively poor. On the basis of simulation calculation, the extraction ability of five crown ethers on Ag(I) and Tl(I) was investigated by solvent extraction. The experimental results showed that the complex constants of five thiacrown ethers for Ag(I) were 3.97, 6.58, 20.61, 9.76, 13.40, respectively in the single system. In the multi-system, thiacrown ethers 2, 3, 4, and 5 had higher extraction rate and selective recognition ability for Ag(I), while thiacrown ether 1 exhibited poor selective recognition ability for Ag(I), this may be due to the small cavity of thiacrown ether 1. However, the five thiacrown ethers had almost no selectivity for Tl(I), this may be related to the coordination properties of Tl(I). Finally, combined with the simulation results and extraction experiments, the extraction mechanism of five crown ethers on Ag(I) and Tl(I) was analyzed in detail.