Objective: The aim of this study was to investigate the clinical manifestations of primary central nervous system lymphoma (PCNSL) with non-immune deficiency and explore effective methods for its diagnosis and treatment. Methods: The clinical, imaging and pathological data from 17 cases with PCNSL in our hospital from March 2006 to April 2009 were analyzed. The immunologic function test for all 17 cases was confirmed as normal. Four of them received stereotactie brain biopsy while the other patients were given full or partial resection. Fifteen of them were given both radiotherapy and chemotherapy after surgery. High-dose Methotrexate (HD-MTX) (2.0g/m2) was used via intravenous infusion once per week for three times. From week 4, patients began radiotherapy. Six cases with abnormal cerebrospinal fluid were given whole central nervous system radiotherapy, and 9 cases with normal cerebrospinal fluid were given only whole brain radiotherapy. Two of them were without any additional treatment after surgery. Sixteen of 17 cases were followed up for 9-48 months. Therapeutic efficacy, toxic and side effect were investigated. Results: Six cases, who were given HD-MTX chemotherapy and whole central nervous system radiotherapy, had grade 3 leukopenia, but other toxic and side effect above grade 3 were not observed. Two patients having no chemotherapy and radiotherapy recurred in one month, but there was only one recurred case in three months among 15 cases who had both chemotherapy and radiotherapy. One of them lost fellow-up. The 2-year survival rate was 69.2%. Conclusion: There is no specific clinical manifestation for PCNSL. The pathological examination is a reliable method to confirm PCNSL. Recurrence may occur after surgery alone, however, the combination of HD-MTX chemotherapy and radiotherapy is an effective and safe therapeutic option, which might improve the treatment efficiency and survival rate. Objective: The aim of this study was to investigate the clinical manifestations of primary central nervous system lymphoma (PCNSL) with non-immune deficiency and explore effective methods for its diagnosis and treatment. Methods: The clinical, imaging and pathological data from 17 cases with PCNSL in our hospital from March 2006 to April 2009 were analyzed. The immunologic function test for all 17 cases was confirmed as normal. Four of them received stereotactie brain biopsy while the other patients were given full or partial resection. Fifteen of them were given both High-dose Methotrexate (HD-MTX) (2.0g / m2) was used via intravenous infusion once per week for three times. From week 4, patients began radiotherapy. Six cases with abnormal cerebrospinal fluid were given whole central nervous system radiotherapy, and 9 cases with normal cerebrospinal fluid were given only whole brain radiotherapy. Two of them were without any additional treatme Six patients, who were given HD-MTX chemotherapy and whole central nervous system radiotherapy, had grade 3 leukopenia , but other toxic and side effect above grade 3 were not observed. Two patients having no chemotherapy and radiotherapy recurred in one month, but there was only only one recurred case in three months among 15 cases who had both chemotherapy and radiotherapy. One of them lost The 2-year survival rate was 69.2%. Conclusion: There is no specific clinical manifestation for PCNSL. The pathological examination is a reliable method to confirm PCNSL. Recurrence may occur after surgery alone, however, the combination of HD- MTX chemotherapy and radiotherapy is an effective and safe therapeutic option, which might improve the treatment efficiency and survival rate.