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Background: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). Methods: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Results: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37–0.61) and PFS (HR, 0.52; 95% CI: 0.36–0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27–0.88) and DFS (HR, 0.49; 95% CI: 0.31–0.68). Conclusion: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies. [ABSTRACT FROM AUTHOR]