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. 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. 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. 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.Copyright © 2020 Li, Zeng, Zhao, Gong and Ma.