Epicatechin (EC) is a well-known dietary polyphenol and widely found in various foods, e.g., apple, cocoa, green tea, wine, etc. Its consumption has been associated with attenuation of some chronic diseases. After ingestion of EC, a large portion is passed into the large intestinal lumen where it is extensively degraded into various microbial metabolites. One of the major EC microbial metabolites is 5-(3’,4’-dihydroxyphenyl)-γ-valerolactone (3,4-diHPV). The protein expression profiles of EC or 3,4-diHPV treated Caco-2 and Hepa1c1c7 cells were studied with the help of label-free quantitative proteomics. Compared to the parent compound EC, 3,4-diHPV was able to induce upregulations of more Nrf2-related proteins in both cell lines, and the number of significant differentially expressed proteins (DEPs) induced by 3,4-diHPV in Hepa1c1c7 cells was much higher than the respective EC treatment.