<p>As hazardous waste generated by the lead and zinc smelting process, acid mud contains a large amount of valuable mercury (Hg) and selenium (Se). In this study, the hydrochloric acid + sodium chlorate‌ (HCl + NaClO₃) leaching system was used to leach the acid mud, and found that the leaching effect of Se and Hg could reach more than 99%. Through X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis, we found that HgSe and Hg₃Se₂Cl₂ were mainly present in the acid mud, and the Se element appeared in the filter residue obtained by the leaching reaction, mainly because the dissolved Se was partially reduced and attached to the filter residue. In addition, the leaching reaction of acid mud conformed to the typical shrink core model (SCM), where chemical reactions were the speed-controlled steps of the entire leaching process for Se and Hg. Combined with FactSage7.1, the entropy (Δ<i>S</i>) and enthalpy (Δ<i>H</i>) of the reaction during the leaching process were obtained as &gt; 0, which verified that the reaction was an endothermic reaction, and the temperature of the reaction system was conducive to the leaching of Hg and Se in the HCl + NaClO₃ leaching system. Notably, the entire leaching process was Gibbs free energy‌ (Δ<i>G</i>) &lt; 0, indicating that the leaching process for Se and Hg were spontaneous. This study included comprehensive characterization technologies, kinetics, thermodynamics, and FactSage7.1 simulation, which may provide a guiding ideology for its subsequent industrial application.</p> Graphical Abstract <p></p>