Abstract: Objective To characterize the changes in the levels of H3K9 acetylation （H3K9ac） around the Nuclear factor-κB （NF-κB） binding site of PNPLA3 gene promoter and the expression levels of related deacetylase （HDAC） and acetyltransferase （HAT） enzymes in the liver of C57BL/6 mice during the fasting/re-feeding transition. Methods According to the weight, 18 C57BL/6 mice were randomly assigned into the ad libitum feeding group （n = 6）, fasting group （n = 6, fasting for 24 h during night） and re-feeding group （n = 6, 24-h fasting followed by ad libitum re-feeding with high sucrose diet for 12 h）. Mice were subjected to fasting/re-feeding interventions. The expression levels of PNPLA3, NF-κB, HDAC （SIRT1, SIRT6） and HAT （GCN5, Elp3） genes were detected and compared among three groups. The H3K9ac enrichment level was assayed by using ChIP-qPCR. Correlation analysis was performed to analyze the relationship between H3K9ac and PNPLA3 expression levels. Results The expression levels of PNPLA3 and NF-κB genes in C57BL/6 mouse liver were significantly down-regulated during fasting and then significantly up-regulated after re-feeding （all P < 0.001）. The changes in the H3K9ac expression level were consistent with those in PNPLA3 （all P < 0.05）. Correlation analysis suggested a significant association between H3K9ac and PNPLA3 expression levels （r_s = 0.958, P < 0.001）. The expression levels of SIRT1 and SIRT6 in the fasting group were significantly higher compared with those in the ad libitum feeding group, which were significantly down-regulated in re-feeding groups （all P < 0.05）, contrary to the changing trend of H3K9ac. The changes in the expression levels of GCN5 and Elp3 were similar with those of SIRT1 and SIRT6 （all P < 0.05）. Conclusions SIRT1 and SIRT6-associated H3K9 deacetylation may be involved in the dietary regulation of NF-κB-driven PNPLA3 expression.