Abstract: Progressive improvements in diagnostic modalities and therapeutic procedures have improved the survival of patients with hepatocellular carcinoma (HCC). However, the incidence of bone metastases in HCC is increasing, and early diagnosis and the development of effective treatment strategies remain global challenges. Thus, it is important to reveal the mechanism of metastasis from HCC to improve the screening and treatment of metastatic disease. Just like other osteotropic cancers, angiogenesis and epithelial-mesenchymal transition play a vital role in bone colonization. Simultaneously, the bone microenvironment enters a vicious circle that can increase bone destruction. To date, prognostic factors and treatment strategies remain unclear for patients with HCC and bone metastases. Future molecular pathological studies will provide further clues as to early diagnosis and individual treatment.