In natural killer/T-cell lymphoma (NKTCL), whole-exome sequencing in 25 patients and subsequent target sequencing in 80 patients show that recurrent mutations are most frequently located in DDX3X (20.0%, 21/105), followed by P53, STAT3, etc. Most of the mutations in DDX3X affect two highly conserved RacA-like domains. Here, DDX3X is linked to extranodal nasal NK/T cell lymphoma.