Hepatocellular carcinoma (HCC) is the fifth most common cancer, with an increasing incidence in recent years. The prognosis is unfavorable, representing the third most frequent cause of cancer-related death worldwide. This is because it generally develops in patients with pre-existing liver pathology, thus limiting therapeutic options. The role of ablative therapies is well-established in nodules smaller than 3 cm, but for nodules from 3 to 5 cm, the best therapeutic management is not well defined. Recent studies reported that combining minimally invasive procedures like transarterial chemoembolization (TACE) with microwave ablation (MWA) or radiofrequency ablation is superior to each alone. However, there is no consensus regarding the timing and the order in which each procedure should be performed. We report a case of an 86 years old male with HCV-related compensated hepatic cirrhosis and multiple cardiac comorbidities diagnosed with a 47/50 mm HCC. Pre-surgical evaluation of the associated pathologies determined that the risk for the surgical approach outweighs the benefits, so the committee decided to treat it in a less invasive manner. We performed MWA and TACE in a single session with technical success according to the modified Response Evaluation Criteria in Solid Tumors (m-RECIST). This case illustrates the first case of simultaneous MWA and TACE performed in our center. This new approach of hepatocellular carcinoma appears to be a good alternative to more invasive methods, with good results even in older people that are unfit for surgery.