Microwave ablation (MWA) is an important method in the treatment of liver cancer. This systematic review compared MWA with liver resection (LR) for liver cancer treatment. In recent years, the MWA has been also reported to play an important role. Studies comparing MWA and LR are lacking. This study aims to compare the efficacy of MWA and LR in the treatment of hepatocellular carcinoma (HCC). A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2019 was conducted for relevant studies that compared the efficacy of MWA and LR in the treatment of HCC. The primary outcomes were local tumor recurrence (LTR) and overall survival (OS) of patients. The secondary outcomes included disease free survival (DFS), extrahepatic metastasis, intrahepatic de novo lesions, length of stay, complications, intraoperative blood loss and operative time. A total of 16 studies including 2622 patients were identified. Incidence of LTR was significantly higher in patients with MWA than LR, with a pooled OR of 2.69 (95% CI 1.33-5.41; P = 0.006). No significant difference in 1-year OS was found. However, patients with MWA experienced higher 3- and 5-year OS, with pooled ORs of 1.40 (95% CI 1.07-1.84; P = 0.01) and 1.41 (95% CI 1.10-1.80; P = 0.007) respectively. In secondary measures, the 1- and 3-year DFS were significantly higher in patients with MWA. However, no significant difference of 5-year DFS was observed. In addition, lower incidence of complications, less intraoperative blood loss and shorter operative time and shorter length of stay were observed in MWA. Though MWA may lead to higher incidence of recurrence, it may be an effective and safe alternative in patients with HCC or liver metastases. MWA may have benefits in patients' survival and safety. Randomized studies should be performed to determine the target population that benefits most from MWA in the future. Copyright © 2020. Published by Elsevier Ltd.