China has the highest morbidity of hepatocellular carcinoma (HCC) in the world. For HCC patients in early stage disease, surgical resection is the best treatment strategy, but most patients in advanced stages lose the opportunity for surgery. Due to the limitations of the current targeted drugs, Sorafenib and Regorafenib, immune brake point drugs provide a potential treatment for patients in advanced stages. CD47 blockade could be a promising strategy for HCC treatment. Although anti-CD47 mAb (Hu5F9-G) is being investigated in patients with solid tumors and Hodgkin’s lymphoma in a phase I trial, the mechanism and efficacy of this approach in HCC need to be further explored.