Abstract: Liquid-liquid phase separation (LLPS) is a process in which certain proteins or protein-RNA complexes form phase-separated droplets with different components and properties through multivalent interactions within a cell. In recent years, the role of LLPS in immunomodulation has received extensive attention. Compared with phase separation-related studies in other fields, limited research has been done on LLPS and the immune system. In this review, we first introduced the basic characteristics of LLPS associated with the immune system, and then explored the functions of LLPS in innate immune-related signaling pathways and adaptive immune cells. LLPS plays a crucial role in immune signal transduction, immune cell activation, and antigen presentation. It is involved in facilitating the aggregation of signaling molecules, regulating the intensity and duration of signal transduction, and influencing the functional state of immune cells. The discovery of LLPS provides a new theoretical basis for elucidating the activation mechanism of the immune system and is expected to bring new perspectives for understanding the cellular defense mechanisms. In-depth investigation of the role of LLPS in the immune system not only helps us gain a more comprehensive understanding of the immune response process, but also provides potential targets and strategies for the development of new immunotherapies and the treatment of autoimmune diseases.