Inflammation is one of the defense mechanisms in our body against pathogens, including bacteria, virus, and parasites. When a bacteria encounters macrophages, which are major immune cells involved in inflammation, it triggers various inflammatory activities of macrophages such as production of nitric oxide and secretion of cytokines to remove the pathogen. However, highly induced chronic inflammatory activity also leads to the tissue damage and sustained cell proliferation stimulated by cytokines, promoting the generation of cancer. Src kinase is a well-known oncogene protein that also involved in inflammation. Src kinase activates transcription factor STAT3, up-regulating cell cycle and cell proliferation, and also phosphorylates AKT which is known to be a major protein maintaining cell survival signaling. In macrophages, Src kinase is not only the oncogene but also one of the major inflammatory signaling proteins that transfer the signal from Toll-like receptor to the transcription factors that regulate the expression of inflammation-mediating genes when the macrophage encounters pathogens. Therefore, Src kinase can be a pharmacological target to regulate both cancer and inflammation. Scutellarein (SCT) is the flavonoid component of Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) is an analog that is synthesized based on the molecular structure of 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), which are able to suppress tumor cell proliferation by inducing apoptosis. Here, I investigated the molecular mechanism underlying the anti-inflammatory and anti-cancer activity of these agents. First, SCT significantly suppressed the secretion of nitric oxide in dose-dependent manner without damaging the cell viability and reduced the iNOS and TNF-? mRNA expression levels in lipopolysaccharide-activated RAW264.7 cells. TRIF-induced NF-?B mediated luciferase activity was also decreased in HEK 293 cells incubated with SCT. In addition, SCT reduced the translocation of NF-?B transcription factor into nucleus in RAW 264.7 cells. Further analysis on the inflammatory signaling proteins revealed that SCT suppressed the activation of kinases including IKK?/?, AKT, p85, which are downstream of Src kinase proteins. The phosphorylation level and enzyme activity of Src were diminished by SCT in LPS-stimulated RAW 264.7 cells, Src-overexpressed HEK cells, and in vitro kinase experiment, indicating that SCT can directly suppress the activity of Src kinase. KTH13-Me strongly diminished the cell viabilities of various cancer cell lines. Several apoptosis markers including morphological changes and chromatin condensing were observed in C6 cells incubated with KTH13-Me, indicating that KTH13-Me can induce apoptosis. Flow cytometry data with C6 cells stained by FITC-Annexin V and PI also put evidence to the pro-apoptotic activity of KTH13-Me. In molecular level, KTH13-Me induced the activation of caspase -3 and -9, and decreased the protein level of Bcl-2. Moreover, the phosphorylation of STAT-3 and Src kinase were diminished in KTH13-Me-treated C6 cells, indicating that the suppression of Src kinase is involved in the pro-apoptotic activity of KTH13-Me. In agree with these results, I conclude that SCT and KTH13-Me have potential to be developed as novel anti-inflammatory and anti-cancer drugs by targeting Src kinase.