Objective To systematically review the efficacy and safety of laparoscopic hepatectomy (LH) and open hepatectomy (OH) for patients with hepatocellular carcinoma (HCC). Methods PubMed, EMbase, The Cochrane Library, CBM, WanFang Data, CNKI databases were electronically searched to collect the case-control studies about LH vs. OH for patients with HCC from inception to December, 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then meta-analysis was performed by using RevMan 5.3 software. Results A total of 28 studies involving 1 908 patients were included. The results of meta-analysis showed that: the LH group was superior to OH group on complications (OR=0.35, 95%CI 0.26 to 0.48, P<0.000 01), hospital stay (MD=–4.18, 95%CI (–5.08, –3.29),P<0.000 01), and five years overall survival rate (OR=1.65, 95%CI 1.23 to 2.19,P=0.000 7) and disease-free survival rate (OR=1.51, 95%CI 1.12 to 2.03, P=0.006). However, no significant differences were found in one year and three years overall survival rate, disease-free survival rate, and postoperative recurrence rate. Conclusion Current evidence shows that the LH is superior to OH for the treatment of HCC, and may be amenable to surgery because of its safety and longtime efficacy. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.