Background and study aim: Percutaneous microwave ablation (MWA) and trans-arterial chemo-embolization (TACE) are established therapies for treatment of HCC patients. Lower rates of complete response with mono-therapies have been reported. Therefore, combined treatment strategies, including combined TACE and MWA have been used. The study aimed at comparing the efficacy of MWA mono-therapy; TACE mono-therapy and combined TACE-MWA in the treatment of 3- 5 cm HCC. Patients and methods: The study prospectively included 102 patients with 113 hepatic focal lesions (3-5 cm) diagnosed as HCC by contrast-enhanced triphasic CT or dynamic MRI. Thirty-five HCC in 34 patients were subjected to MWA mono-therapy; 41 HCC in 34 patients were subjected to TACE mono-therapy, while 37 HCC in 34 patients were subjected to combined TACE-MWA therapy. Follow up by contrast-enhanced CT or MRI was done at one month, and every 3 months, up to one year after treatment. Therapeutic tumor response and local tumor progression were evaluated and compared among the groups. Results: After one year follow up, the combined TACE-MWA group showed a higher rate of complete response (CR) (83.3%) when compared to MWA group (76.5%) and TACE group (66.6%) (P>0.05). The local tumor progression (LTP) rate in the combined TACE-MWA group was lower (16.6%) than that in MWA group (23.5%) and TACE group (33.3%) (P=0.2). Conclusion: Combined TACE-MWA therapy appears to be non-significantly superior to MWA mono-therapy and TACE mono-therapy in terms of complete tumor response and local tumor progression in patients with 3-5 cm HCC.