Abstract Appropriate biomarkers may help predict patient response to treatment for extranodal natural killer/T‐cell lymphoma (ENKTL), a subtype of non‐Hodgkin's lymphoma in China. Programmed cell death receptor 1 (PD‐1) and its ligand (PD‐L1) have been investigated in various tumors. However, few studies have addressed expression of PD‐1/PD‐L1 in peripheral blood of ENKTL patients. To identify novel peripheral blood biomarkers for diagnosis and treatment of ENKTL, we retrospectively examined 89 healthy volunteers, 49 patients with ENKTL and 74 patients with diffuse large B‐cell lymphoma treated at West China Hospital from September 2017 to September 2018. Both patient groups showed significantly higher expression of PD‐1 and PD‐L1 on CD4+ T cells, higher levels of PD‐L1 mRNA in peripheral blood mononuclear cells (PBMCs) and higher levels of soluble PD‐L1 in plasma than healthy volunteers ( P < .05). In ENKTL patients, levels of PD‐L1 mRNA and soluble PD‐L1 were related to disease stage, level of lactate dehydrogenase, lymphocyte count, and copies of Epstein‐Barr genome in blood. Levels of PD‐L1 mRNA and soluble PD‐L1 were similar between healthy volunteers and ENKTL patients who showed complete remission after treatment, and uni‐ and multivariate analyses identified soluble PD‐L1 as a predictor of treatment response in ENKTL patients. Our results suggest that the levels of PD‐L1 mRNA in PBMCs and soluble PD‐L1 in plasma are useful for ENKTL staging and prediction of treatment response.