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Isoflavones are commonly found in diets, such as soybean and clover. Their anti-inflammatory effects are due to the inhibition of the transcriptional regulation of NF-κB. Hydrogenated isoflavones are metabolites of isoflavones with higher bioavailability, however, there have been few studies on their anti-inflammatory effects. In this work, by using the LPS-stimulated RAW264.7 cell model, we investigated the anti-inflammatory effect and the underlying mechanism of hydrogenated isoflavones. Hydrogenated isoflavones reduced the production of LPS-stimulated pro-inflammatory mediators and enzymes, including TNF-α, IL-6, NO, iNOS and COX-2. The level of ROS was also diminished in LPS-stimulated RAW264.7 cells. Further mechanistic studies showcase that hydrogenated isoflavones block NF-κB and MAPK pathways via attenuation of p65 nuclear translocation and JNK, ERK, and p38 phosphorylation, respectively. In addition, we found that hydrogenated isoflavones display anti-proliferation effect in human colon cancer cells with wild-type p53. Together, hydrogenated isoflavones could be used as an adjuvant for the treatment of inflammation and cancer. [Display omitted] • Hydrogenated isoflavones are metabolites of soybean isoflavones with anti-inflammatory immune effect. • Hydrogenated isoflavones inhibit LPS-stimulated inflammation via attenuation of NF-κB and MAPK pathways. • Hydrogenated isoflavones inhibit the proliferation of human colon cancer cells with wild-type p53. • Hydrogenated isoflavones could be as an adjuvant for the treatment of inflammation and cancers. [ABSTRACT FROM AUTHOR]