The demand for nickel resources has increased significantly in recent years due to the large-scale application of high-nickel ternary lithium batteries in the field of new energy electric vehicles. To alleviate the shortage of nickel resources in China, the nickel extraction from nickel-containing minerals has received widely attention. As an important nickel-containing minerals, the composition of nickel sulfide ore is complex and it is difficult to be leaching under atmospheric conditions. Therefore, green, high efficient, and low-cost technologies for extracting nickel from nickel sulfide ore resources have attracted much attention. In this work, the mechanical activation was introduced to increase the reactivity of nickel sulfide ore, then Na2S2O8 was used to leaching activated nickel sulfide ore under atmospheric conditions. Various conditions including rotation speed, ball-to-material ratio and ball milling time as well as the acid concentration, oxidation concentration, leaching time, liquid-to-solid ratio, stirring rate and temperature in the leaching process were optimized and the mechanism was further discussed. It was found that the mechanical activation process reduced the particle size and increased the degree of amorphization of nickel sulfide ore resulting in an increase in its reactivity, and the leaching process converted part of the S2- to sulfur by Na2S2O8 reducing the release of harmful gas H2S during the reaction. At the optimal conditions (rotation speed of 613 r/min, ball-to-material ratio of 20:1, ball milling time of 120 min, acid concentration of 2 mol/L, Na2S2O8 concentration of 0.42 mol/L, leaching time of 60 min, liquid-to-solid ratio of 5:1, stirring rate of 400 r/min and temperature of 80℃), leaching rate of Ni, Co, Cu and Fe were 98.9%, 97.7%, 98.2% and 98.7%, respectively, while the content of Ni, Co and Cu in residues were 0.45%, 0.03% and 0.14%, respectively. With this research, it was expected to provide theoretical and technical support for the efficient extraction of valuable metals from nickel sulfide ores.