Amyl xanthate (AX), a widely used reagent in sulfide mineral flotation, has caused serious environmental problems. Manganese dioxides (MnO2), ubiquitous in natural soils and sediments, are one kind of important oxidant or catalyst in facilitating organic pollutant decomposition. In this study, the oxidative degradation of AX by MnO2 was investigated in batch experiments. It was found that up to 90% AX was decomposed by MnO2 in 30 min and the removal efficiency of AX depended strongly on the loading of MnO2 and pH value in the solution where the reactions closely followed a pseudo-first-order model. The reaction orders with respect to the initial AX concentration, MnO2 concentration and pH value were 0.4573, 0.2034, and −0.1701, respectively. Coexisting metal ions, such as Mn2+, Fe3+, Ca2+ and Mg2+, displayed suppressive effects and the inhibitive capacity of the metal ions followed the order Mn2+ > Fe3+ > Ca2+ > Mg2+. However, the effect of humic acid (HA) on reaction rates was significant only at higher concentrations. This study provided meaningful information to elucidate the oxidative degradation of AX by MnO2.