This study investigated the curative effect of cryoablation combined with molecular target therapy for advanced non-small cell lung cancer (NSCLC). Thirty-six female patients with NSCLC and epidermal growth factor receptor gene mutations were randomly divided into two groups: 18 patients received the molecular target therapy gefitinib (group I), an epidermal growth factor receptor-tyrosine kinase inhibitor; and 18 patients were treated with cryoablation prior to the administration of gefitinib (group II). Treatment with gefitinib was continued for 6 months. Compared with group I, the rates of partial regression, stabilization of disease and progression of disease were improved in group II at the end of the 6 months of gefitinib treatment. Moreover, the 1-year survival rate in group II was significantly higher than that in group I. This suggests that cryoablation therapy combined with gefitinib could improve the effects of treatment and the prognosis of patients with advanced NSCLC.