Background and AimMolecular‐targeted agents such as lenvatinib and sorafenib have been approved to treat hepatocellular carcinoma (HCC). However, the choice between these two agents in the primary treatment for advanced HCC is still under debate with conflicting results. We sought to evaluate the efficacy of lenvatinib and sorafenib in patients with HCC.MethodsWe performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until February 10, 2023. The primary outcome of this meta‐analysis was overall survival (OS). The secondary outcomes were progression‐free survival (PFS), time to progression, objective response rate (ORR), and disease control rate (DCR).ResultsA total of 13 studies with 3705 patients (1635 on lenvatinib and 2070 on sorafenib) were included in our analysis. The mean age of the patients in both groups was comparable (66.81 vs 65.9 years). Pooled analysis of primary outcomes showed that, compared with sorafenib, lenvatinib was associated with significantly better OS in patients treated with these drugs (HR 0.82, 95% CI: 0.69–0.97, P = 0.02). Pooled analysis also showed that PFS (HR 0.67, 95% CI: 0.57–0.78, P < 0.00001) and time to progression (HR 0.49, 95% CI: 0.31–0.79; P = 0.004) were significantly better in the lenvatinib group compared to the sorafenib group. It also showed that the lenvatinib group had significantly better ORR (odds ratio [OR] 5.43, 95% CI: 3.71–7.97; P < 0.00001) and DCR (OR 2.35, 95% CI: 1.75–3.16; P < 00001) than the sorafenib group.ConclusionOur study shows that lenvatinib is superior to sorafenib regarding OS and PFS in patients with advanced HCC.