Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma. The predominant subtype is diffuse large B-cell lymphoma (DLBCL), and no systematic lesion is identified at diagnosis. BTKi (Bruton's tyrosine kinase inhibitor) has demonstrated significant clinical activity in DLBCL. We retrospectively reported on 2 patients who began with memory deterioration or right limb movement disabilities. A cranial magnetic resonance imaging (MRI) scan and a brain biopsy were used to diagnose PCNSLs. Middle-dose methotrexate (MD-MTX) regimens were initiated for induction treatment. Zanubrutinib was chosen as the maintenance regimen due to the patients' inability to tolerate continuous MTX regimens. For 1 patient, he achieved sustained complete remission (CR) demonstrated by MRI. Another patient achieved partial remission (PR). The two patients are both alive until now. We successfully extended the PFS and OS in elderly PCNSL patients treated with zanubrutinib.