As a newly discovered ICI, Siglec-15 is widely expressed in various tumor cell types, and PD-1/ PD-L1 expressions is mutually exclusive. Siglec-15 may be a new therapeutic target for PD-1/ PD-L1 as a treatment option for patients who do not respond to therapy. This review discusses the recent research of the characteristic pathways of Siglec- 15, its involvement in immune regulation mechanisms, and its tumor-related expression. Clinical application of an anti- Siglec-15 antibody was analyzed, and the therapeutic prospect of Siglec-15 for NSCLC treatment is discussed.