The present invention relates to a method for treating a subject suffering from a liver disease comprising a step of administering said subject with a therapeutically effective amount of an inhibitor of the endoribonuclease activity of IRE1?. Inventors have shown that in livers of tunicamycin-treated BI-1-/- mice aIRE1?-dependent NLRP3 inflammasome activation, an hepatocyte death, a fibrosis and a dysregulated lipid homeostasis that led to liver failure within a week. To test whether the pharmacological inhibition of IRE1? endoribonuclease activity would block the transition to NASH, mice were injected with the small molecule STF-083010 twice a week for 2 weeks towards the end of a 3-month HFD. In BI-1-/- mice, STF-083010 treatment effectively counteracted IRE1? endoribonuclease activity, improving glucose tolerance and rescuing from NASH. The hepatocyte-specific role of IRE1?’s RNase activity in mediating NLRP3 inflammasome activation and programmed cell death was confirmed in primary mouse hepatocytes through knockdown experiments and with STF-083010.