The invention relates to a space-level nuclear electromagnetic interference resistant data bus cable and a manufacturing method thereof. The space-level nuclear electromagnetic interference resistant data bus cable comprises two insulated wire sets, two tubular filling cores, a shielding layer and a sheath, wherein the insulated wire sets are formed by wrapping an insulating layer outside multiple conductors in an extruded manner, the two insulated wire sets and the two tubular filling cores are stranded to form a cable, and the shielding layer is arranged outside the cable and wrapped by the sheath in an extruded manner. The shielding layer is in a three-layer structure, both an inner shielding layer and an outer shielding layer are weaved silver-plated copper wire shielding layers, a middle shielding layer is a wrapped nuclear electromagnetic interference resistant nickel-based alloy composite tape shielding layer in a three-layer structure, both a first layer and a third layer are polyimide film shielding layers, and a second layer is the nuclear electromagnetic interference resistant nickel-based alloy composite tape shielding layer. The manufacturing method includes steps: firstly, conductor processing; secondly, insulation processing; thirdly, tubular filling core processing; fourthly, stranded cable processing; fifthly, shielding layer processing; and sixthly, sheath processing. The space-level nuclear electromagnetic interference resistant data bus cable has the advantages of light weight, high nuclear electromagnetic interference resistance, radiation resistance, atomic oxygen resistance and good thermal vacuum outgassing.