Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease, and no standard treatment and validated prognostic model were established. Serum sIL-2R alpha levels were measured in 94 ENKTL patients to evaluate its relationship with clinical features, treatment response, and prognosis. Serum sIL-2R alpha level was 2964 +/- 1613.6 ng/L in ENKTL patients, higher than in normal healthy controls (p < 0.05). Using median level (2508.5 ng/L) as cutoff, patients were divided into higher-and lower-level group (N = 47 for each). The complete remission and overall remission rate were significantly higher in lower-level group (p < 0.05). After a median follow-up time of 22.0 months, 2-year overall survival and progression-free survival rates were 60.0 and 53.0 %, respectively. Lower sIL-2R alpha level significantly correlated with better progression-free survival (PFS) and overall survival (OS) (p = 0.001 and 0.002, respectively). IPI score and treatment responses after 2 cycles of chemotherapy significantly correlated with PFS and OS (p < 0.05). In a multivariate Cox regression model that included IPI score, treatment responses, and sIL-2R alpha level, all three parameters were independent prognostic factors for OS (p = 0.043, 0.001, and 0.025, respectively), and the last two parameters were also independent factors for PFS (p = 0.005 and 0.005, respectively). Elevated serum sIL-2R alpha level was related to poor responses to treatments and can be used as a valuable biomarker for disease activity. Moreover, serum sIL-2R alpha was an independent prognostic factor for both OS and PFS. These results need to be validated in prospective trials and may support the incorporation of anti-CD25 targeted therapy into the treatment realm of ENKTL.