Hepatocellular carcinoma is the most common form of primary liver cancer which is the fifth most common cancer in men and the seventh in women and the third most common cause of cancer-related death worldwide. Only 10–20% of patients are eligible for curative treatments that result in a 5-year survival rate of 40% to 70%. Therefore, the development of novel treatment options is necessary for the majority of patients and remains a considerable challenge. Conformal radiotherapy is used in certain circumstances and preliminary data obtained from phase 1/2 trials are showing promising curative effects. There is thus an interest in identifying drugs that can be exploited to enhance radiation sensitivity that could be used in therapy and might improve clinical outcome. Small molecules inhibitors of poly(ADP-ribose) polymerases (PARP) are an example of a radio- and chemo-sensitizing drug, as well as being an efficient single agent treatment in certain genetic backgrounds. In this review, we discuss the role of PARP-1 in hepatocellular carcinoma and present the results of preclinical studies that have assessed the potential of PARP inhibition as a single treatment or combined with chemotherapy or radiotherapy for the treatment of hepatocellular carcinoma.