Objective: To investigate the curative effect and safety of ultrasound-guided microwave ablation combined with transcatheter arterial chemoembolization (TACE) in the treatment of advanced primary liver cancer in special parts. Methods: One hundred and twenty patients with advanced primary liver cancer in special parts who were admitted to the hospital during the period from January 2015 to January 2018 were selected. They were divided into the control group and the observation group by the random number table method, 60 cases in each group. The control group was treated by TACE alone while the observation group was treated by ultrasound-guided microwave ablation combined with TACE. The therapeutic effects, liver function indexes [serum total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT) and albumin (Alb)], postoperative complications, length of hospital stay, hospitalization costs, postoperative 6-month, 1-year and 2-year survival rates were compared between the two groups. Results: The effective rate of treatment in the observation group was higher than that in the control group (86.67% vs 68.33%) (P<0.05). Levels of TBIL, DBIL and ALT in the observation group were lower than those in the control group after treatment (P<0.05), and the level of Alb was higher than that in the control group (P<0.05). There was no significant difference between the two groups in the incidence of postoperative nausea and vomiting, fever or liver pain (P>0.05). The length of hospital stay and hospitalization costs of the observation group were longer/more than those of the control group (P<0.05). The postoperative 6-month, 1-year and 2-year survival rates of the observation group (95%, 90.00%, 80.00%) were higher than those of the control group (80.0%, 75.00%, 61.67%) (P<0.05). Conclusion: Ultrasound-guided microwave ablation combined with TACE is effective in the treatment of advanced primary liver cancer in special parts. It can significantly improve the liver function and short-term survival rate of patients.