Abstract: The diffusion of solutes in reactor pressure vessel (RPV) steel, accompanied with point defects, will result in the formation of precipitation and segregation on grain boundary, which will cause the hardening and embrittlement of materials. In order to deeply understand the performance degradation of RPV steel, the knowledge on solute diffusion mechanism is required. The vacancy-mediated diffusion mechanism of major solutes in RPV steel was studied by molecular dynamics method. Firstly, solute-vacancy interactions were studied. Subsequently, based on multi-frequency model, the vacancy drag factor and diffusion coefficient were calculated. The results show that Cu and P have strong binding energies with vacancies both in the first nearest neighbor (1nn) and the second nearest neighbor (2nn), and Ni has stronger binding energy with 2nn vacancy than 1nn vacancy. The vacancy drag factor increases with temperature, which means that solutes diffuse by exchanging with vacancy at high temperature.