Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor worldwide. Due to the heterogeneity nature, prognosis for patients with HCC remains unsatisfactory. The conventional treatments like chemotherapy and radiotherpay fails to cure the disease most of the time and this may be due to the presence of cancer stem cells (CSCs). Cancer stem cell is a small population of cancer tissues responsible for chemoresistant, radioresistant, and cancer relapse through various mechanism like ATP binding cassete (ABC) effulus and ALDH inhibitor. Numores cancer stem cell markers are idendified for the liver cancer, such as Epithelial cell adhesion molecule (EpCAM), CD133, CD90, CD13. EpCAM is one of the first tumor-associated antigen and a marker for most epithelial cancers except renal cell carcinoma, urothelial carcinoma and squamous cell carcinoma. Also it is a marker for liver stem cells/progenitor cells. EpCAM plays a major role in cell-cell migration, cell proliferation, tumorogenisity, metastasis. Also, it acts as a potential target for EpCAM positive carcinomas like breast cancer, colon cancer and liver cancer. This entire review deals about how EpCAM can be used in the near future as a potential therapeutic target for HCC.