Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo. These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.