Accordingly, in the present study, we found that inhibition of XOR by febuxostat alleviates pathological manifestations in a MASLD rat model, including hepatic lipid accumulation, serum metabolic disorders, and systemic oxidative stress, and this effect coincides with reduced JNK phosphorylation and enhanced NRF2 and HO-1 protein expression. This evidence concerns the gene NFE2L2 and metabolic dysfunction-associated steatotic liver disease.