New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.