Here, we showed that Icaritin abolished primary and secondary hepatosphere formation of HCICs, reduced the populations of cells positive for HCC-stem cell markers such as EpCAM, inhibited primary and secondary xenografts in NOD/SCID mice, suppressed malignant growth of the primary HCC cells, Hep-12 in vitro and in vivo. Here, EPCAM is linked to hepatocellular carcinoma.