Objective: Extranodal natural killer /T-cell lymphoma (ENKTL) is an aggressive and unusual subtype of non-Hodgkin lymphoma (NHL) that it is related with the Epstein-Barr virus (EBV). CSF is considered as an ideal source of high-concenrtation disease-related proteins. We aimed at identifying the proteomic markers changes of CSF in ENKTL patients and used such changes to diagnose ENKTL. Materials and methods: In this study, CSF samples were acquired from hospitalization patients from the Cancer Center of West China Hospital, Chengdu, China. Comparative proteomic profiling are commonly used to do label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). And in this study the same method was used to characterize the variety of proteins in ENKTL patients and none-ENKTL people. Results: In the aggregate, 421 non-excrescent and functional proteins were identified among the samples. Of these proteins, 45 proteins quantified match the involved criteria. HRG, TIMP-1, SERPINA3, FGA, FGG, TF, FGB, APP, and AGT were significantly up-regulated. Discussion: We discovered that some proteins were significantly up-regulated. Also, these proteins themselves or with others proteins may be potential markers to diagnose ENKTL. The changes of proteomics may be a potential method to precisely identify the pathogenesis of the ENKTL.