Abstract: Primary immune-privileged site large B-cell lymphoma (IP-DLBCLs) is a general term introduced in the 5th edition of the World Health Organization (WHO) Classification of Lymphoid Tumors and refers to a group of aggressive B-cell lymphomas that originate in sites behind the immune barrier in immunocompetent patients. Anatomical-derived immune sanctuaries (such as the blood-brain, blood-retinal, and blood-testicular barriers) and immunomodulatory systems that share the same immunophenotype and molecular characteristics currently include the central nervous, vitreoretinal, and testes systems and large B-cell lymphomas. The primary immune-privileged site large B-cell lymphoma prognosis is relatively poor, with no standard treatment plan. Toll-like receptor-mediated nuclear factor kappa B (NF-κB) (via MYD88 mutation) and B-cell receptor (BCR) (via CD79B mutation) pathway activation was the core pathogenesis mechanism in all three systems (central nervous, vitreoretinal, and testes), presenting a potential common treatment target. Bruton's tyrosine kinase (BTK) is a central molecule in the above signaling pathway, thus BTK inhibitors present a reasonable therapeutic drug choice for such diseases. This article reviews the mechanism of action, clinical studies, adverse reactions, and drug resistance of BTK inhibitors in primary immune-priviledged site large B-cell lymphoma treatment.