Because of the excessive complexity, range and heterogeneity of tumor incidence and improvement, multi-mode synergy remedy is simpler than single therapy mode to enhance antitumor efficacy. And the multifunctional probe is essential to synergy remedy. Herein, a multifunctional DNA tetrahedron nanoprobe was ingeniously designed to concurrently obtain chemodynamic remedy (CDT) and gene silencing for synergy antitumor. The multifunctional DNA tetrahedron nanoprobe, DNA tetrahedron-silver nanocluster-antagomir-21 (D-sgc8-DTNS-AgNCs-Anta-21), built-in CDT reagent (DNA-AgNCs), miRNA-21 inhibitor (Anta-21) with focused recognition probe (aptamer) collectively. After focused getting into most cancers cell, D-sgc8-DTNS-AgNCs-Anta-21 silenced endogenous miRNA-21 by Anta-21and produced extremely poisonous ·OH by reacting with H2O2, which induced the apoptosis of tumor cells. The focused recognition of aptamers led to the concentration-dependent demise of HeLa cells. Quite the opposite, the cell survival charge of regular cells was mainly unaffected because the focus of D-sgc8-DTNS-AgNCs-Anta-21 will increase. Moreover, the in vivo therapy confirmed that D-sgc8-DTNS-AgNCs-Anta-21 had good in vivo anti-tumor efficacy and could be a promising synergistic antitumor agent with negligible hostile results to regular organs or tissues. Due to this fact, the varied features, biocompatibility and programmability of DNA present a helpful and simple strategy to meeting multifunctional probe for synergy remedy.