Our data revealed the following: (1) DDX3X translocates from the cytoplasm to the nucleus during Con A-induced liver injury; (2) DDX3X deficiency protects mice from Con A-induced liver injury by regulating ER stress; (3) the nuclear translocation of DDX3X transcriptionally induces CHOP under ER stress; and (4) DDX3X translocates into the nucleus in the liver tissues of HBV-LF patients and AIH patients. Here, DDIT3 is linked to Lassa fever.