Screening out combined amendments, which can simultaneous immobilize cadmium (Cd), lead (Pb), arsenic (As) and have little effect on the availability of medium and trace elements, can provide a scientific basis for the remediation the acidic multi-heavy metals contaminated soil. A soil culture experiment was conducted to investigate the effectiveness of sepiolite (S), ferro-manganese ore powder (F) and biochar (B) and their combinations on the availability of Cd, Pb, As, zinc (Zn), iron (Fe) and manganese (Mn) in acidic multi-heavy metals contaminated soil at the same dose (6 g/kg soil). The results showed that sepiolite, Fe-Mn ore powder, biochar and their combinations increased soil pH and decreased the available concentrations of Cd, Pb and As in soil. The effectiveness of combined treatments on reducing the availability of Cd, Pb and As was better than that of single treatments. The three amendment materials and their combinations reduced the availability of Zn to a certain extent, and the three amendment materials and most of their combinations reduced the availability of Fe and Mn. The efficiency of simultaneous immobilization of Cd, Pb and As by S5F1B0 combination was relatively high. Compared with the control, the concentration of available Cd, Pb, As, and Zn in soil treated with S5F1B0 was reduced by 30.9%, 84.5%, 60.2% and 32.5%, respectively, while the concentration of available Mn was increased by 19.9%. The concentration of available Cd, Pb, Zn, and Mn were significantly negatively correlated with pH. The combination of S5F1B0 had a high efficiency of simultaneous immobilization of Cd, Pb, and As in the multi-heavy metals contaminated soil, which could appropriately improve the Mn availability, and Zn should be properly supplied when the combination is applied.