Here, using high-fat-diet-induced NAFLD mouse model and PA-induced cell model, we focused on the antioxidant and anti-inflammation effect of CA and tried to connect and explain the crosstalk among AMPK, keap1/Nrf2, and NFκB system in HFD-induced NAFLD for the first time. This evidence concerns the gene NFKB1 and metabolic dysfunction-associated steatotic liver disease.