Objective To investigate the therapeutic effect and adverse effects of the teniposide-based regimen in patients with primary central nervous system lymphoma (PCNSL). Methods Between March 2011 and July 2013, 16 patients with PCNSL were diagnosed and treated. The clinical characteristics, diagnosis,therapy, results and adverse effects were analyzed. Results Totally 16 patients were enrolled and diagnosed as primary central nervous system diffuse large B-cell lymphoma. All patients received teniposide-based regimen chemotherapy and 9 patients received teniposide plus rituximab. The overall response rate was 87.5 % (14/16), including 10 cases of CR and 4 cases of PR. With a median follow-up of 13.5 months, the progression-free survival (PFS) and overall survival (OS) rates of 2 years were 29.9 % and 66.7 %, respectively. The mainly hematological adverse events were neutropenia, including grade 3 in 4 cases (25 %) and grade 4 just in one case. There was one case of treatment related death. Conclusions The response rate of teniposide-based regimen for PCNSL is promising. The 2 year PFS and OS rates are even higher than results of traditional high-dose methotrexate regimen. The teniposide-based regimen is well tolerated, and the adverse events are acceptable.