We have demonstrated that ctDNA assessment could predict the therapy response in NKTCL, and the highest mutation frequencies were in KMT2D, APC, ATM, ASXL3, JAK3, SETD2, TP53, NOTCH1. Our results could define the optimal strategy for patient follow-up. Here, SETD2 is linked to extranodal nasal NK/T cell lymphoma.