[MoS4]2- clusters were bridged between CoFe layered double hydroxide (LDH) layers using the ion-exchange method. [MoS4]2-/CoFe-LDH showed excellent Hg0 removal performance under low and high concentrations of SO2, highlighting the potential for such material in S-Hg mixed flue gas purification. The maximum mercury capacity was as high as 16.39 mg/g. The structure and physical-chemical properties of [MoS4]2-/CoFe-LDH composites were characterized with FT-IR, XRD, TEM&SEM, XPS, and H2-TPR. [MoS4]2- clusters intercalated into the CoFe-LDH layered sheets; then, we enlarged the layer-to-layer spacing (from 0.622 to 0.880 nm) and enlarged the surface area (from 41.4 m2/g to 112.1 m2/g) of the composite. During the adsorption process, the interlayer [MoS4]2- cluster was the primary active site for mercury uptake. The adsorbed mercury existed as HgS on the material surface. The absence of active oxygen results in a composite with high sulfur resistance. Due to its high efficiency and SO2 resistance, [MoS4]2-/CoFe-LDH is a promising adsorbent for mercury uptake from S-Hg mixed flue gas.