Hepatocellular carcinoma (HCC) is a common cancer with high incidence and mortality worldwide. The main treatments for HCC include radical hepatectomy, liver transplant, locoregional therapies, and systemic therapies. Systemic treatments include targeted agent treatment, chemotherapies, antiviral therapies, and nutritional treatments. According to the results of SHARP and ORIENTAL study, sorafenib became the standard first-line therapy since 2008 because of nearly three months of survival improvement in patients with advanced HCC. Subsequent studies on targeted agents found that neither sunitinib nor brivanib were superior to sorafenib as first-line therapy. After progression or intolerance of sorafenib, brivanib did not improve the overall survival (OS) compared with placebo as second-line therapy. Randomized controlled EACH study and retrospective AGEO study for systemic chemotherapy showed that oxaliplatin-based or gemcitabine-based regimen was effective for advanced HCC patients. Randomized controlled trial for adjuvant chemotherapy in China showed that capecitabine could reduce the risk of recurrence and improve postoperative survival of HCC. Comparing sorafenib with other treatments, several retrospective studies found that other treatments were not inferior to sorafenib in terms of OS. In the systemic treatment of HCC, antiviral treatment can decrease the recurrence of HBV-related HCC postoperation and prolong the survival of patients. Based on the etiology, symptoms, complications, and treatment-related side effects, nutritional treatment is also very important for HCC patients. Systemic chemotherapy, newer targeted agents, and immune therapy are the new directions in future research.