ObjectiveTo evaluate systematically the effectiveness and safety of transcatheter arterial chemoembolization (TACE) in combination with lenvatinib (LEN) in the treatment of intermediate and advanced primary liver cancer (PLC). MethodsThe relevant literature was comprehensively searched in the CNKI, VIP, Ovid, Schopus, PubMed, and other databases from the establishment of the databases to March 14, 2023. The literature was obtained according to the search strategy and the inclusion and exclusion criteria, and the data were extracted and the literature quality was evaluated. The Revman 5.4 software and Stata 15.1 software were used to conduct the meta-analysis to evaluate the effect of TACE+LEN regimen on the objective response rate (ORR), disease control rate (DCR), overall survival (OS), as well as secondary outcome indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha fetoprotein (AFP), and hypertension, diarrhea, hand-foot disease, fatigue, proteinuria, and fever for the patients with PLC. ResultsA total of 15 relevant literature was included, including 1 219 patients with PLC, 591 of whom treated with TACE+LEN and 628 treated with TACE alone. The meta-analysis results showed that the TACE+LEN regimen could increase ORR and DCR and prolong OS (P<0.01), as well as effectively decrease AFP level (P<0.01). However, TACE+LEN regimen increased the risks of hypertension, diarrhea, hand-foot disease, fatigue, and proteinuria as compared with TACE alone treatment (P<0.05). However, there were no statistical impacts on AST and ALT, or the risk of fever (P>0.05). ConclusionFrom the results of this meta-analysis, TACE+LEN regimen has a certain efficacy in treatment of intermediate and advanced PLC, but prevention of its related complications is paid attention to.