The interstitial defects play a crucial role in controlling the irradiation performance of high-entropy alloys (HEAs) particularly of CrMnFeCoNi. However, the site-to-site chemical and magnetic disorder of HEAs prohibits understanding the behavior of interstitials in HEAs. Herein we demonstrate that the chemical bonding dominates the formation of dumbbells at the weak magnetic effect, whereas the strong magnetic effect can perform over the chemical bonding in determining the formation of dumbbells. Accordingly, Ni-containing dumbbells are particularly unstable due to its weak chemical bonding and magnetic effect, while the spin-down Cr and the magnetic adaptive Mn are essential for stabilizing CrMnFeCoNi. Note that the chemical bonding and magnetic effects can be quantitatively characterized by the cohesive and band-filling descriptors. Our study elucidates a physical understanding of the dumbbell interstitials of HEAs and provides a rational guidance for designing advanced structural alloys with optimal irradiation resistance.