Hepatocellular carcinoma is a serious threat to global health. Surgery remains the best curative therapy but only a small number of patients may benefit. Non-surgical therapies are playing an increasingly important role for hepatocellular carcinoma. In this chapter, the authors aim to review the current non-surgical approaches to hepatocellular carcinoma, including transcatheter arterial (chemo) embolization, cryoablation, percutaneous ethanol injection, radiofrequency ablation, and interstitial laser coagulation, with a special emphasis on the molecular basis of these therapies. Understanding the underlying biological and molecular mechanisms of hepatocellular carcinoma will not only help surgeons to refine existing techniques, but may also help us develop novel therapeutic approaches.