Hepatocellular carcinoma (HCC) annually causes about one million deaths. Because of advanced stage at diagnosis, HCC carries a five-year survival rate of less than 5% in patients diagnosed with unresectable disease. Incidence for HCC is higher in men and individuals of Asian descent, where viral hepatitis, a leading cause of HCC, is endemic. This article will provide an overview of the complex symptom management of patients with HCC. The occurrence of multiple symptoms, including pain, fatigue, weight loss, and obstructive syndromes (e.g., ascites, jaundice) in patients with HCC is common. Because of limitations in the efficacy of current treatment options, aggressive symptom management is key to preserving physical functioning and quality of life in patients with HCC. A multidisciplinary team approach to symptom management of patients with HCC is critical, with oncology nurses playing an integral role.