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A number of studies in the recent years have evaluated the anti-proliferative activity of flavonoids. Although certain studies investigated the structure–activity based on the phenotypic assays, no study has correlated the flavonoids structure with the ability to alter gene/protein expression. Present study was focused to understand the structure–function relationship of citrus flavonoids in terms of their ability to alter the gene expression in the colon adenocarcinoma cells. Eight structurally related flavonoids found in citrus were evaluated for their ability to inhibit colon cancer (SW480) cells, as well as change the expression of apoptosis related genes/proteins. Apigenin and quercetagetin demonstrated most significant inhibition of cell proliferation with 63.6% and 45.7% inhibition of cell growth at 200μM after 48h of incubation, respectively. The cell death was also confirmed by images of fluorescently tagged cells …