The clinical benefits and safety of Sorafenib versus hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) are inconsistent in some studies. This meta-analysis aims to evaluate the effectiveness and safety of Sorafenib versus HAIC for patients with advanced HCC. An electronic search was performed from PubMed, Embase, the Cochrane Library and Web of Science to identify comparative studies evaluating Sorafenib versus HAIC for HCC. Objective response rate, disease control rate, overall survival, progression-free survival and adverse events were evaluated using meta-analytical techniques. Fourteen retrospective studies with 1779 patients (Sorafenib = 773, HAIC = 1006) were included in the meta-analysis. HAIC delivered favorable outcomes in objective response rate (odds ratio 0.13; 95%CI, 0.07-0.24) and disease control rate (odds ratio 0.48; 95%CI 0.26-0.87) assessed by the Response Evaluation Criteria in Solid Tumors. The pooled hazard ratio for overall survival at 0.60 (95% CI 0.39-0.91) and the pooled hazard ratio for progression-free survival at 0.69(95% CI 0.51-0.95), further indicates that HAIC was superior to Sorafenib. There was a higher incidence of adverse events, including hypertension (odds ratio 13.07; 95% CI 2.37-71.67), fatigue (odds ratio 6.72; 95% CI 2.14-21.13), dermatological disorders (odds ratio 15.87; 95% CI 5.58-45.16) and gastrointestinal disorders (odds ratio 3.20; 95% CI 2.02-5.07) in patients receiving Sorafenib than in those receiving HAIC. HAIC offers a safe and effective alternative to Sorafenib with better tumor response and longer overall survival and progression-free survival, hence HAIC should be recommended for the patients with advanced HCC.