Notably, besides its regulation of tumorigenesis, DUSP22HepOE dramatically repressed the pathological features of NASH, including hepatic steatosis, fibrosis, F4/80-mediated inflammatory cell infiltration, and inhibited HCC cell proliferation proved by the decreased Ki-67-positive staining compared to the DUSP22HepRosa mice post DEN/HFHC treatment, accompanied with the reduced expression of inflammation- and fibrosis-related genes via the blockage of its downstream FAK, ERK1/2, and NF-κB signaling pathways. Here, NFKB1 is linked to fatty liver disease.