The inactivation of tumor suppressor gene positive regulatory domain containing I (PRDM1) and activation of signal transducer and activator of transcription 3 (STAT3) have been detected in the majority of extranodal NK/T‑cell lymphoma, nasal type (EN‑NK/T‑NT) cases. In the present study, their association with and effects on the clinicopathologic features of EN‑NK/T‑NT are described. PRDM1 was revealed to be expressed in 19 out of 58 patients (32.8%) with EN‑NK/T‑NT, and phosphorylated STAT3 was overexpressed in 42 out of 58 (72.4%). Oncogenic pathways were investigated by NanoString encounter technology in 5 PRDM1(+) and 5 PRDM1(‑) EN‑NK/T‑NT specimens. Multiple oncogenic pathways involved in cell apoptosis, cellcycle (CC) and angiogenesis were discriminately activated in EN‑NK/T‑NT cases, and in PRDM1(+) cases in particular. The sustained activation of the Janus kinase 3 (JAK)/STAT3 pathway was more pronounced. In addition, missense mutations in the SRC homology 2 domain of STAT3 were detected in 7 out of 37 EN‑NK/T‑NT cases (18.92%), and the acquired mutation was related to the activation of the JAK3/STAT3 pathway. The downregulation of PRDM1 and upregulation of phospho‑STAT3 (Tyr705) were associated with angiocentric infiltration of EN‑NK/T‑NT (P=0.039). Notably, the prognosis of patients in the PRDM1(+)/STAT3 [mutated (mut‑)] group was considerably improved than that of patients in the STAT3(mut+)/PRDM(‑) group (P=0.037). In addition, the inhibition of NK/T cell lymphoma cell lines by Stattic and tofacitinib could suppress cell proliferation by inducing cell apoptosis or arresting the CC. The present results revealed that the JAK3/STAT3 oncogenic pathway and PRDM1 expression could stratify clinicopathologic features of EN‑NK/T‑NT. The inhibition of the JAK3/STAT3 pathway may serve as a treatment option for EN‑NK/T‑NT.