Propolis, which is a complex resinous material has diverse pharmacological and biological properties. Phase I and II enzymes are responsible for detoxication and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in metabolic activation of xenobiotics. This study was designed to investigate the in vitro modulatory effects of Anatolian propolis and its phenolic contents; caffeic acid, quercetin and p-coumaric acid on the mRNA expression levels of CYP1A1, CYP1A2, CYP2E1, NQOI, GSTP1 and GPx in human colorectal adenocarcinoma HT-29 cells. Analysis results revealed that the propolis extract and its major phenolic contents; caffeic acid and quercetin suppressed the mRNA expression levels of CYP1A1, CYP1A2 and CYP2E1 between the range of 1,66 and 4,55 fold, while p-coumaric acid did not show remarkable effects on the enzymes aforementioned. On the other hand, the extract and all phenolics increased the mRNA expression levels of antioxidant enzymes; NQO1, GSTP1 and GPx between the range of 1,51 and 9,85 fold. This preliminary study demonstrates that phenolic content rich-Anatolian propolis modulates the gene expression of the enzymes involved in xenobiotics activation and detoxication pathways.