Mode-coupling theory is developed and employed to compute the nanoparticle diffusion coefficient in polymer solutions. Theoretical results are compared with molecular dynamics simulation data for a similar model. The theory properly reproduces the simulated effects of the nanoparticle size, mass, and concentration on the nanoparticle diffusion coefficient. Within the mode-coupling theory framework, a microscopic interpretation of the nonmonotonic dependence of the diffusion coefficient on the nanoparticle concentration is given in terms of structural and dynamic effects. Both the size dependence and mass dependence of the diffusion coefficient indicate a pronounced breakdown of the Stokes-Einstein relation for the present model.