The partitioning of the alloying elements into the γ″ nanoparticles in a Ni2CoFeCrNb0.15 high entropy alloy was studied by the combination of atom probe tomography and first-principles calculations. The atom probe tomography results show that the Co, Fe, and Cr atoms incorporated into the Ni3Nb-type γ″ nanoparticles but their partitioning behaviors are significantly different. The Co element is much easier to partition into the γ″ nanoparticles than Fe and Cr elements. The first-principles calculations demonstrated that the different partitioning behaviors of Co, Fe and Cr elements into the γ″ nanoparticles resulted from the differences of their specific chemical potentials and bonding states in the γ″ phase.