Abstract: As a new type of alloy system, high entropy alloy, due to its structural and performance characteristics different from traditional alloys, is capable of forming simple solid solution. Thus, its research has become a hot spot in recent years. Gap atoms can dissolve into the matrix lattice gap to produce solid solution strengthening, by combining with alloy elements to form fine dispersion strengthening phase and reducing stacking fault energy and changing dislocation motion mode, which greatly improves the properties of high entropy alloy. This paper analyzes the effects of interstitial atoms C, N, O and B on the formation law, strengthening mechanism and plastic deformation mechanism of high-entropy alloys on the basis of discussing the microstructure characteristics of high-entropy alloys. The research progress of interstitial atoms content and its effects on the microstructure and properties of high-entropy alloys, such as solution strengthening, grain refinement and second-phase strengthening, are summarized. In addition, we put forward a new research direction of microstructure design of high-strength high-toughness high-entropy alloys containing interstitial atoms.