[Abstract]ObjectiveTo investigate the therapeutic effect of argon-helium cryoablation combined with sorafenib on hepatitis B-related advanced hepatocellular carcinoma (HCC)and to evaluate the role of microvessel density (MVD) in prognostic evaluation. MethodsA total of 102 patients with advanced HCC were randomly divided into two groups, with 50 receiving sorafenib plus cryoablation(group S&C) and 52 receiving only cryoablation (group C). The endpoint of the treatment was tumor progression or untolerable adverse reaction. Tumor tissues were obtained before treatment. MVD was evaluated by immunohistochemical analysis using CD34 antibody. The therapeutic effects were evaluated according to RECIST criterion every 4-6 weeks. The adverse events were observed in both groups; the therapeutic effect, overall survival time(OS), and time to progression(TTP) were compared between two groups. MethodsIn group S&C, complete response (CR) was achieved in 2 patients(4%), partial response(PR)in 9 (18%), and stable disease(SD) in 22(44%), with the disease control rate(DCR) being 66%; in group C, no CR, PR in 4(7.6%), and SD in 19(36.5%), with the DCR being 44.2% (P<0.05). The overall survival (OS) and the time to progression (TTP) were significantly longer in group S&C than in group C (12.5 months vs 8.6 months, 9.6 months vs 5.3 months; P<0.01). The mean MVD in group CR&PR (111/0.74 mm2)was significantly lower than that in group PD(339/0.74 mm2, P<0.01). Patients with lower MVD receiving sorafenib plus cryoablation had longer OS and TTP than those only receiving cryoablation. The OS and TTP in patients with higher MVD had no significant difference between different groups. MethodsSorafenib plus cryoablation is a safe and effective therapy for patients with advanced HCC; it can improve the OS and TTP of patients. Patients with higher MVD have a lower response to therapy and poor prognosis.