AIM: To evaluate the effectiveness and safety of percutaneous hepatic cryoablation in combination with percutaneous ethanol injection (PEI) in patients with unresectable hepaocellular carcinoma (HCC).METHODS: A total of 105 masses in 65 HCC patients underwent percutaneous hepatic cryoablation.The cryoablation was performed with the Cryocare system (Endocare, Irvine, CA, USA) using argon gas as a cryogen.Two freezethaw cycles were performed, each reaching a temperature of-180 at the tip of the probe.PEI was given in 36 patients with tumor masses larger than 6 cm in diameter 1-2 weeks after cryoablation and then once per week for 4 to 6 sessions.The efficacy was evaluated with survival, change of tumor size and alpha-fetoprotein (AFP) levels.RESULTS: During a follow-up duration of 14 months in average with a range of 5 to 21 months, 33 patients (50.8 %) were free of tumors, 22 patients (33.8 %) alive with tumor recurrence: two had bone metastases, three were found to have lung metastases, and the remaining 17 recurrences occurred in the liver, of whom only 3 developed a cryosite recurrence.Among the 41 patients who were followed up for more than one year, 32(78 %) were alive despite of tumor recurrence.Seven patients (10.8 %) died due to disease recurrence.Three patients (4.6 %) died due to some noncancer-related causes.Among the 43 patients who had a CT scan available for review, 38 (88.4 %) had a shrinkage of tumor mass.Among the 22 patients who received biopsies of cryoablated tumor mass, all biopsies except one, showed only dead or scar tissues.Of the patients who had an increased AFP preablatively, 91.3 % had a decrease of AFP to normal or nearly normal levels during postablative 3-6 months.Complications of cryoablation included liver capsular cracking in one patient, transient thrombocytopenia in 4 patients and asymptomatic right-sided pleural effusions in 2 patients.Two patients developed liver abscess at the previous cryoablation site at 2 and 4 months, respectively, following cryoablation, and was recovered after treated with antibiotics and drainage.CONCLUSION: Percutaneous cryoablation offers a safe and possibly curative treatment option for patients with HCC that cannot be surgically removed, and its integration with PEI, may serve as an alternative to partial liver resection in selective patients.