Abstract: Objective To explore the efficacy and safety of argon-helium knife cryotherapy combined with transcatheter arterial chemoembolization （TACE） on huge hepatocellular carcinoma. Methods Eighty-five patients with huge liver cancer from September 2006 to August 2011 were analyzed retrospectively. Observation group （n=44） received one to two TACE and one to three argonhelium knife cryotherapy after one month sequently， while the control group （n=41） received TACE treatment only. Response to chemotherapy was assessed by RECIST criteria 1.0 and follow-up data was investigated. Results The response rate of observation group was 70.5％， higher than 46.3％ of the control group （P＜0.05）. The 1-， 2-， 3-year survival rates of observation group were 77.3％， 56.8％ and 36.4％， and medium overall survival time was 19.2 months， which were all higher than the 51.2％， 36.6％， 14.6％ and 11.8 months of control group （P＜0.05）. The adverse reaction of both groups were mild-to-moderate and tolerable. Conclusion Argon-helium knife cryotherapy combined with TACE has synergism effect and minimally invasive， and provide a new regiem for comprehensive treatment on huge hepatocellular carcinoma.