Objective To explore the clinical application value of transcatheter arterial chemoembolization (TACE) combined with CT-guided percutaneous acetic acid injection (PAI) in treatment of huge hepatocellular carcinoma (HCC). Methods Forty-three patients with huge HCC were randomly divided into two group. Twenty-one patients in group A underwent routine one course for TACE (three times), and the interval of TACEs was one month. Twenty-two patients in group B underwent TACE combined with PAI, and CT-guided PAI was performed once a week since 2-3 weeks after first TACE, and one course included 6-9 times of PAI. Postoperative follow-up was conducted (including AFP, the size of tumor, etc.). One course of treatment was repeated in case of tumor recurred. Results At the 1st month after treatment, no statistical difference was found of AFP positive rate between two groups. Statistical difference of total effective rate was found between two groups (38.10% vs 77.27%). The 1-, 2- and 3-year survival rate In group A was 47.62%, 23.81% and 9.52%, respectively, while in group B was 81.82%, 54.55% and 36.36%, respectively, and significant differences were found between the two groups for the same period. Conclusion TACE combined with PAI is safe and more effective than TACE alone in the treatment of huge HCC.