The effect of annealing on magnetotransport and structural properties of Ni70Co30/Cu multilayers is investigated. The GMR signal remains stable up to 175 °C and almost disappears at 285 °C. The total resistivity of multilayers is nearly constant below 175 °C and rapidly increases after annealing at 285 °C. By the combination of x-ray reflectivity, x-ray diffuse scattering and extended x-ray absorption fine structure (EXAFS) techniques, it is found that Ni atoms and Cu atoms occupy preferentially the interfacial position of the multilayer and the interface roughness is mainly caused through the diffusion of Cu and Ni in the grain boundary during the deposition. After 285 °C annealing, the interface roughness increases remarkably and the interfacial lateral correlation length and the fractal exponent of Co, Ni and Cu decrease significantly. At the same time, the differences in the interfacial lateral correlation lengths of Co, Ni and Cu also becomes smaller. This suggests that the intermixing of adjacent layers takes place. It can be concluded that the degradation mechanism of the GMR effect on the annealed Ni70Co30/Cu multilayer is the compositional mixing at the interfaces, rather than the interlayer diffusion of atoms along the grain boundary.