AKT1 is a member of the serine/threoine AGC protein kinase family involved in thyroid cancer metabolism,growth, proliferation and survival. It is overexpressed in thyroid tumors. In this study, we designed two AKT1specific DNAzymes (DRz1 and DRz2) that target AKT1 mRNA. The results showed that DRz1 could decreasethe expression of AKT1 by 58%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosisand inhibited invasion in SW597 cells. In addition, down-regulation of survivin expression was associated withdecreased caspase-3, VEGF and MMP2 in SW597 cells after 24 h. In our study, the efficacy of DRz1 in decreasingAKT1 protein levels were better than DRz2. AKT1-DRz1 might have anti-tumorigenic activity and may providethe basis for a novel therapeutic intervention in thyroid cancer treatment.