Caffeic acid (CA) is a natural polyphenol containing carboxylic acid found in many herbs, and known as an anti‐inflammatory, anti‐tumorigenic and anti‐cancer effect in vitro and in vivo. And cytochrome P450 1A1/2 (CYP1A1/2) are members of the cytochrome P450 superfamily of enzymes involved in xenobiotic and metabolism. These enzymes play a major role in bioactivation of polycyclic aromatic hydrocarbons (PAHs) and other environmental pro‐carcinogens into their carcinogenic forms. Because of this, the accumulations of CYP1A1/2 remain a focus of interest in cancer research and food toxicology. Phase II enzymes such as heme oxygenase‐1 (HO‐1) and quinone reductase (QR) catalyze conjugation by sulfation, glucuronidation, and neutralize electrophilic chemicals to facilitate elimination of activated chemical compound by CYP1A1/2. In this study, we investigated the potential ability of CA to induce CYP1A enzymes in HepG2 human hepatoma cells. Our results showed that CA increases CYP1A1/2 mRNA expression dose‐dependently. Also gene expressions of HO‐1 and QR (phase II enzymes), were significantly up‐regulated with CA treatment. Thus, these data suggest that CA has potentials of enhancing capacity on CYP1A1/2 expressions (phase I enzymes) and also increasing HO‐1 and QR enzymes (pahse II enzymes), and may prove to be an effective chemopreventive agent.