Background and Aims Hepatocellular carcinoma (HCC) is one of the common malignant tumors. Transarterial chemoembolization (TACE) and transarterial embolization (TAE) are common treatment options for unresectable HCC. In recent years, hepatic arterial infusion chemotherapy (HAIC) has been used to treat advanced HCC and has achieved satisfactory therapeutic effects. However, few studies directly compare HAIC with TACE/TAE. Therefore, this study was conducted to evaluate the efficacy and safety of HAIC and TACE/TAE in the treatment of unresectable HCC.Methods The studies on HAIC and TACE/TAE in the treatment of unresectable HCC published as of 14 August 2021 were searched in PubMed, OvidSP, Cochrane Library, Web of Science, Wanfang Database, CNKI, and VIP Chinese Journal Database. The data relevant to the outcome variables such as overall survival (OS), disease-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events were extracted, and Meta-analysis was performed using Review Manager 5.4 software.Results A total of 5 studies were finally included. Results of Meta-analysis showed that HAIC group was superior to TACE/TAE group in terms of OS (HR=0.39, 95% CI=0.18-0.86, P=0.02), ORR (RR=3.82, 95% CI=2.41-6.04, P<0.000 01) and DCR (RR=1.52, 95% CI=1.12-2.05, P=0.006). Moreover, the results were still consistent after exclusion of possible sources of heterogeneity by sensitivity analysis. There was no significant difference between HAIC group and TACE/TAE group in PFS (HR=0.34, 95% CI=0.11-1.04, P=0.06), but the PFS in HAIC group was better than that in TACE/TAE group after exclusion of possible sources of heterogeneity (HR=0.56, 95% CI=0.43-0.73, P<0.000 1). For any grade of adverse events, the risk ratios of thrombocytopenia (RR=1.59, 95% CI=1.04-2.44, P=0.03) and diarrhea (RR=4.57, 95% CI=2.01-10.37, P=0.003) were higher, while the risk ratios of elevation of alanine aminotransferase (RR=0.57, 95% CI=0.35-0.92, P=0.02) and hyperbilirubinemia (RR=0.37, 95% CI=0.26-0.53, P<0.000 01) were lower in HAIC group than those in TACE/TAE group; for grade 3-4 adverse events, the risk of leukopenia in HAIC group was higher than that in TACE/TAE group (RR=6.32, 95% CI=1.71-23.28, P=0.006); for either grade 3-4 adverse events or any grade, the risk of fever in the HAIC group was lower than that in the TACE/TAE group (P<0.05); there were no significant differences in incidence rates of anemia, neutropenia, and hypoproteinemia as well as abdominal pain and vomiting between the two groups (all P>0.05).Conclusion Compared with TACE/TAE, HAIC offers better tumor response and longer survival, and acceptable adverse reactions. So, it is a better treatment option for patients with unresectable HCC.