Objective: To study the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous acetic acid injection (PAI) on massive hepatocellular carcinoma (MHCC). Methods: TACE was performed in 57 patients with MHCC, which were randomly divided into group A (n = 28) and group B (n = 29). Patients in the group Areceived conventional TACE for the first time and then received low dose TACE (10 mg mitomycin C) for the repeated treatment, Re-examined CT scans after TACE for a week. Based on filled status of Lipiodol in the Lesions, PAI was underwent in the area of rarefaction or defect filled by Lipiodol. Patients in the group B received conventional TACE. Then The survival rate and masses variation and hepatic function and α-FP and side effects were observed. Results: The 1-, 2- and 3-year survival rate after TACE were 96.4%, 78.6%and 32.1% for group A, and 65.5%, 48.3% and 20.7% for group B. Masses diminution were found in all patients in group A, while 20 cases were found in group B, unchanged in 5 cases and enlarged in 4 cases. Conclusion: The efficacy of TACE combined with PAI are significantly better than that of TACE only, low dose TACE produces less hepatic damage and less side effect.