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Aim To evaluate the safety and efficacy of transarterial chemoembolization(TACE)combined with cryoablation in patients with large hepatocellular carcinoma(HCC).Methods This is a retrospective study involving 122 patients with unresectable large HCC admitted to The First Affiliated Hospital of Sun Yat-sen University between November 2011 and July 2015.The patients were divided into study group(58 patients who underwent TACE combined with cryoablation)and control group(64 patients who underwent TACE alone).Adverse reactions,laboratory examination,short-term effect of the initial treatment,long-term effect and prognostic factors for survival were statistically analyzed.Result There was no statistic difference in general information between two groups.A few mild or moderate major adverse reactions occurred in study group,but all were cured after treatment.There was no significant difference in incidence of minor adverse reactions between two groups.In comparison with control group,the changes of some items of peripheral hemogram and liver function in study group were more obvious on the first day after treatment,but after one month the median change rates of all items in both groups were less than 10%compared with baseline level.The effective rates of study and control group were 29.3%and 10.9%,respectively(P=0.011),and the control rates were 79.3%and 62.5%,respectively(P=0.042).The median survival time was 11.0 months(95%CI: 7.4,14.6)for study group and 5.0 months(95%CI: 4.0,6.0)for control group.The 6-,12-,and 18-month overall survival rates for study and control group were 84.5%,49.5%,26.8%and 48.1%,17.8%,11.1%,respectively(P<0.01).On multivariate analysis,negative distant metastasis,Barcelona Clinic Liver Cancer B-stage,neutrophil-to-lymphocyte ratio≤5,alpha fetoprotein<400μg/L,combined treatment and effective initial treatment were independent protective factors for survival of patients with large HCC.Conclusions TACE combined with cryoablation is an effective and safe treatment option compared with TACE alone for patients with unresectable large HCC,and the prognosis of the patients is affected by multiple factors.