Nonalcoholic fatty liver disease (NAFLD) has become one of the most concerning health problems in the world. Dietary intervention is an effective way to prevent and improve NAFLD. As one of the main metabolites of anthocyanins, protocatechuic acid (PCA) exhibited strong activity to improve NAFLD, but the specific mechanism remains unclear. Currently, proteomics has been used to identify that PCA treatment could significantly influence the expression of 224 proteins, including 89 downregulated proteins and 135 upregulated proteins. KEGG analysis showed that PCA obviously inhibited the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Immunofluorescence and Western blot analyses further confirmed that PCA repressed the protein expression of PPARγ and subsequently inhibited the expression of free fatty acid (FFA) uptake proteins (CD36 and FABP2) and FFA synthesis proteins (ACC and FASN), respectively. These effects of PCA contributed to the inhibitory activity of excessive lipid accumulation in the liver. Our results highlighted that PCA could effectively alleviate high-fat diet-induced (HFD) NAFLD by inhibiting lipid absorption and synthesis through the PPARγ signaling pathway.