The low surgical resection rate and high postoperative recurrence rate of hepatocellular carcinoma(HCC) are urgent clinical problems to be solved. Therefore, it is important to develop effective perioperative treatment. In recent years, a growing number of studies have shown that systemic therapy is expected to break through the limitations of traditional local treatment and play an important role in preoperative treatment. For example, some novel targeted agents and immunocheckpoint inhibitors have shown excellent potential as neoadjuvant treatment for HCC. Meanwhile, researchers have explored the application of systemic therapy as adjuvant therapy, but due to different criteria for patient selection, no consensus is reached on its efficacy. By far, there is no standard procedure for the application of systemic therapy in HCC perioperative period, little is known about the efficacy and safety of targeted drugs and immunotherapy. This article discusses the feasibility of systemic therapy as neoadjuvant and adjuvant treatment of HCC, as well as its adverse events, with an aim to provide new horizons of HCC systemic therapy in the perioperative period.