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RATIONALE AND OBJECTIVES To investigate the technical success, safety and outcomes of transcatheter arterial chemoembolization (TACE) combined with simultaneous cone-beam computed tomography (CBCT)-guided microwave ablation (MWA) in small hepatocellular carcinoma (SHCC). MATERIALS AND METHODS Retrospective analysis of 66 lesions in 50 patients (38 men, 12 women) who underwent TACE combined with simultaneous CBCT-guided MWA for SHCC. After 1 month of treatment, the tumor responses were assessed using the mRECIST criteria, along with interventional-related complications and changes in hepatic and renal function. Moreover, progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS All patients achieved technical success. The mean target tumor size was 3.4 ± 0.7 (range, 2.2-4.9) cm. The mean energy, ablation duration per tumor, and the mean safety margin were 51.3  ±  8.4  kJ, 6.7  ±  0.8  minutes and 1.4 ± 0.6 cm, respectively. The 1-, 3-, and 5-year PFS rates were 90.0%, 65.4%, and 35.7%, respectively, with a mean PFS of 43.46 months; and the 1-, 3-, and 5-year OS rates were 98.0%, 89.8%, and 74.3%, respectively, with a mean OS of 54.90 months. Multivariate Cox regression analysis further illustrated that TACE combined with MWA in the treatment of a single tumor with a diameter of less than 3 cm was an independent protective factor for PFS and OS (p < 0.001). The patients had no major complications. Among the exceptions, one patient (2%) had an asymptomatic perihepatic effusion that resolved spontaneously, two patients (4%) developed massive right pleural effusion, requiring thoracic drainage, and another patient (2%) developed a hepatic subcapsular hemorrhage required interventional embolization. CONCLUSION CBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of SHCC with a high technical efficacy.