Objective: To investigate the efficacy and clinical value of transcatheter arterial chemoembolization (TACE) combined with ultrasound-guided microwave ablation for the treatment of liver cancer in special sites. Methods: The patients with liver cancer in special sites (the liver cancer was adjacent to the gallbladder, dome of diaphragm, gastrointestinal tract, heart, great vessels, and portal vein, with the shortest distance from the tumor to the organ/lumen < 0.5 cm ) were enrolled as treatment group, and the patients with primary liver cancer in normal sites treated in our hospital during the same period were randomly enrolled as control group. They underwent TACE combined with ultrasound-guided microwave ablation. The 6-month, 12-month, 18-month and 24-month survival rates of the patients in two groups were analyzed. Results: The clinical data of 40 patients with liver cancer in special sites, including 9, 7, 5, 11, 3, 3, and 2 patients with liver cancer adjacent to the gallbladder, dome of diaphragm, gastrointestinal tract, portal vein, hepatic vein, inferior vena cava, and heart, respectively, and another 40 patients in control group were collected in the study. The negative rate of alpha-fetoprotein (AFP) was 83.3% in the treatment group and 82.8% in the control group. The 6-month, 12-month, 18-month, and 24-month survival rates were 100.0%, 95.0%, 90.0%, and 80.0%, respectively, in the treatment group, and 100.0%, 97.5%, 92.5%, and 85.0%, respectively, in the control group. Conclusion: TACE combined with ultrasound-guided microwave ablation is as effective for liver cancer in special sites as for those in normal sites, with high safety, and is feasible in clinical application.