Abstract INTRODUCTION In primary central nervous system lymphoma (PCNSL), various cytokines and chemokines are known to be elevated in cerebrospinal fluid (CSF). In this study, we investigated the relationship between CSF IL-10 and IL-6 concentrations and prognosis. METHODS The patients with PCNSL who underwent treatment with MTX from 2008 to 2024 were analyzed. IL-10, IL-6, b2-microglobulin (MG), and sIL-2 receptor (sIL-2R) were measured preoperatively. we analyzed the relationship between CSF concentration d each cytokines and overall survival (OS) or progression-free survival (PFS). RESULTS A total of 67 patients (38 males, 29 females) were included, with an average age of 66 years and an average KPS of 72. Thirty-six patients received MTX + RT therapy, and 31 patients received R-MPV therapy. CSF IL-10, IL-6, b2-MG, and sIL-2R levels were 505±2133pg/ml, 20.5±40.4pg/ml, 4059±:1730ug/l, and 377±621U/ml, respectively. When the cutoff value for IL-6 was set at 8pg/ml, the PFS was significantly longer in the high CSF IL-6 group than in the low CSF group (p=0.026). When the cutoff value for IL-10 was set at 80pg/ml, the high CSF IL-10 group tended to have a longer PFS than the low CSF group (p=0.06). Multivariate analysis of PFS revealed that CSF IL-6 (p=0.0003), CD10 expression (p=0.0078), and pretreatment KPS (p=0.026) were significant prognostic factors. Multivariate analysis of OS revealed that CSF IL-6 (p=0.015), CD10 expression (p=0.043), and treatment (p=0.046) were significant prognostic factors, with CSF IL-6 being a significant prognostic factor for both OS and PFS. CONCLUSION Patients with high CSF IL-6 concentrations had significantly longer survival times, but CSF IL-10 was not. IL-6 is a proinflammatory cytokine with diverse effects, and PCNSL with high IL-6 levels may be more responsive to treatment.