The decomposition of plant litter in soil changes soil nutrient content and plays an important role in regulating soil pH and availability of potentially toxic elements (PTEs). However, there remains limited studies on the mechanism under which litter influences the transport of PTEs in the process of ecological restoration. This study examined the effect of plant litter decomposition mediated reduction of iron and sulfur components on migration of PTEs from mercury-thallium mine waste. The results showed that the four kinds of litter alleviated the acidity of the waste, especially the Bpa and Tre litter. The nitro and nitroso groups produced by the decomposition of the litter were adsorbed onto the waste, thereby providing an electron transfer medium for iron reducing microorganisms, such as Geobacter. This promoted the reduction and release of Fe3+ to Fe2+ and reduced the electronegativity (El) value of waste. The reduced El promoted the adsorption of metal cations such as Hg and Tl to maintain electrical neutrality. However, it was not conducive to the adsorption of oxygen containing anions of As and Sb. An increase in litter resulted in an increase in reductivity of mercury-thallium mine waste. This maintained the reduction of Fe3+ to Fe2+ and changed or destroyed the structure of silicate minerals. PTEs, such as Tl, Hg, As, and Sb, were released, resulting in reductions in their residual fraction. However, the strong reduction conditions, especially the decomposition of Bpa, caused part of the released Hg(II) combining with S2− produced by the reduction of SO42− to form insoluble HgS, thereby reducing its migration. The findings could provide a theoretical basis to guide the situ-control and ecological restoration of PTEs in waste slag site.