Background: Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) intervention in prolonging the long-term survival and prognosis of patients with liver cancer are still controversy compared with the traditional interventional therapy of RFA alone. This meta-analysis aimed to compare the efficacy and safety of combination therapy versus RFA alone. Methods: The related articles were searched in PubMed, Embase, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Science and Technology Journal Database, and China Biomedical Literature Database (CBM). The Chinese and English search keywords included transcatheter arterial chemoembolization, TACE, radiofrequency ablation, RFA, primary liver cancer, and liver tumor. The five evaluation criteria of randomized controlled trials (RCTs) in Cochrane RoB 2.0 repeatedly independently evaluated the bias risks involved in the study and cross-checked the results. Results: A total of 7 articles were included, and the results of bias risk assessment show that 6 articles described the generation of random sequences in detail; There were 3 articles describing allocation concealment in detail; Operator blindness was used in 4 articles; The outcome indicators of 7 documents were complete. The 3-year overall survival rate of the RFA combined with TACE group was significantly better than that of the RFA group [odds ratio (OR) =1.97, 95% confidence interval (CI): 1.42-2.74, Z=4.05, P<0.0001]. The 1-year and 3-year tumor recurrence-free survival rates in the RFA combined with TACE group were significantly better than those in the RFA group (OR =1.88, 95% CI: 1.28-2.76, Z=3.23, P=0.001; OR =2.11, 95% CI: 1.37-3.24, Z=3.38, P=0.0007). There was no significant difference in the complication rate of patients with primary liver cancer between the RFA combined with TACE group and the RFA group (OR =0.79, 95% CI: 0.45-1.39, Z=0.81, P=0.42). Discussion: Meta-analysis results confirmed that TACE combined with RFA was safe and effective in the treatment of primary liver cancer, and can improve the overall survival and recurrence-free survival of patients with primary liver cancer.