Our findings showed that dysregulation of the α1-Na/K-ATPase signalosome in NASH-related HCC is associated with concomitant downregulation of the α1-NKA subunit, upregulation of the anti-apoptotic protein survivin, and downregulation of the pro-apoptotic SMAC protein expression, promoting a cell fate ‘switch’ from apoptosis to mitosis, which drives cell proliferation and tumorigenesis. Here, DIABLO is linked to metabolic dysfunction-associated steatohepatitis.