AIM: This study assesses the effectiveness of combining transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in treating hepatocellular carcinoma (HCC). METHODS: Retrospective analysis of 125 HCC patients treated from 2020 to 2021, divided into two groups: monotherapy using TACE (n = 63), and a combined approach of RFA and TACE (n = 62). Comparison factors included clinical efficacy, liver function, tumor markers, complications, quality of life, and prognosis. RESULTS: The combined treatment group showed higher effectiveness (p < 0.05), improved liver function and tumor marker levels 4 weeks post-treatment (p < 0.05), significantly fewer complications (p < 0.05), and enhanced quality of life at the year-long follow-up (p < 0.05). The prognosis was better in the combination group, demonstrated by fewer recurrences and higher 1-year survival rates (p < 0.05). CONCLUSIONS: The dual approach of TACE and RFA shows improved results for HCC patients, including improved liver function, reduced tumor markers, fewer complications, and superior quality of life and prognosis. Consequently, combined treatment approach is endorsed for clinical practice.