Background and Aims: There are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus tran-shepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). There-fore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC. Methods: A total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups. Results: Thirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3％, 77.8％ and 66.7％ in the HR group and 80.6％, 72.2％ and 52.8％ in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6％, 57.3％ and 42.3％ in the HR group and 66.1％, 45.8％ and 39.3％ in the CK-SBRT+TACE group, re-spectively (OS: p=0.143; PFS: p=0.445). Both a high plate-let count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS. Conclusions: CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.