Objective To systematically review the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) and sorafenib (SORF) separately or combined in the treatment of advanced hepatocellular carcinoma (HCC). MethodsWe searched the PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases for studies on HAIC and SORA separately or in combination in the treatment of advanced HCC from inception to November 1, 2021. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 software. ResultsA total of 21 studies involving 2 501 patients were included. The results of meta-analysis showed that the overall survival (OS) (HR=0.46, 95% CI 0.25 to 0.87, P=0.02), objective response rate (ORR) (OR=4.00, 95%CI 2.74 to 5.85, P<0.000 01) and disease control rate (DCR) (OR=2.20, 95%CI 1.30 to 3.75, P=0.004) were higher in the HAIC group than the SORF group, while the incidence of adverse reactions was not increased. However, HAIC combined with SORF showed no significant difference in OS, ORR, DCR or progression-free survival (PFS) compared with SORF alone. Moreover, combined treatment increased the adverse reactions of blood system. Conclusion The current study suggests that HAIC can improve OS, ORR and DCR in patients with advanced HCC; however, there is no additional benefit when combining SORF with HAIC. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.