The present disclosure provides a low-molecular-weight Tremella aurantialba glucuronoxylomannan (LTAG) as well as a preparation method and an application thereof, and specifically relates to the technical field of medicine. The LTAG provided in the present disclosure has a weight-average molecular weight of 8,000-24,000 Da. In the method of preparing LTAG as provided in the present disclosure, Tremella aurantialba glucuronoxylomannan is depolymerized by peroxides so as to get low-molecular-weight products, which are then exchanged into pharmaceutically acceptable salts through cation exchange resins. The resulting LTAG has a clear structure, a low viscosity and a good solubility, has a strong immune-enhancing activity, and is capable of acting on TLR4 receptor-activated macrophagocytes and promoting the production of various immune factors, so it can be used in the prevention and/or treatment of immunodeficiency-related diseases.