In NAFLD&NASH, we observed that oxidative stress could activate epidermal growth factor receptor (EGFR) to facilitate (i) UBC to repress HSF1 in the WNT and MAPK signaling pathways; (ii) APP to activate ETS1 in the MAPK signaling pathway to induce DNA repair function through the mediation of RFC5, to activate metabolism through the mediation of TRMT1, and to inhibit apoptosis through the mediation of ZNF480; and (iii) SHC1 to repress STAT5A in the MAPK signaling pathway. Here, RFC5 is linked to metabolic dysfunction-associated steatohepatitis.