In order to develop an efficient resonance self-shielding method that can model the complex resonance-interference effects in depleted fuel compositions, an improved Pseudo Resonant Isotope Model (PRIM) has been developed by incorporating a number density–perturbation technique in the resonance cross-section tables for pseudo isotopes. Numerical results for homogeneous mixtures, pin cells, and pressurized water reactor lattice problems show that the new model is able to produce accurate group cross sections for a wide range of depletion states of different types of fuels, comparable to those obtained from online ultra-fine-group slowing-down calculations. Computational cost analysis shows that the improved PRIM is a promising method applicable to the resonance self-shielding calculations for large-scale reactor core analysis with depletion.