The invention discloses a device and a method for operating low-refractive-index-medium nano-particles, which belong to the optical capturing and optical micro operating technology field. The device comprises a laser, a beam expanding lens group, a polarization converting device, a reflection lens, a beam splitting device, a space light modulator, a diaphragm, an oil immersed object lens, and a displacement station. According to the invention, the method comprises: through the polarization converting device and the space light modulator, generating a radial polarization vortex light field with complicated distribution of the space position phases; and under the focusing of the oil immersed lens, using two-row oppositely-transmitted light field interference to generate hollowed spherical focusing spots which can capture the low-refractive-index-medium particles located within the focusing field in the center of the focusing field in a three-dimensional manner stably. Through the change in the focusing conditions and the space light modulator's loading position phases, it is possible to realize the operation to multiple particles and the flexible regulation and control to the motion trajectories of the particles. The method overcomes the problem in the traditional optical tweezing technology that capturing low-refractive-index-medium particles in a three-dimensional manner is impossible. The method can be widely applied in a series of fields related to the optical operations.