Naringenin has been shown to display various biological effects such as antioxidant, anticancer, anti-inflammatory, and antiviral activities. Taxifolin inhibits the production of lipopolysaccharide-induced prostaglandin E, and fustin suppresses the activity of acetylcholinesterase. They all belong to flavanone which is a class of flavonoids with a C6-C3-C6 skeleton. Since the anticancer activities of flavanone derivatives have rarely been reported, we examined the effects of 26 flavanone derivatives on HCT116 colorectal cancer cells. Our results suggest that flavanone derivatives control the expression of cell cycle regulatory proteins, which blocks G1 cell cycle progression and inhibits the clonogenicity of HCT116 cells. In addition, in order to design flavanone derivatives that show better anticancer activity, structure-activity relationships were examined.