The ability to manipulate and intervene in the processes of assembly and disassembly of DNAs and nanoparticles is important for the exploitation of nanoparticles in medical diagnostics and drug delivery. This report describes the results of an investigation of a strategy to intervene in the assembly and disassembly processes of DNAs and gold nanoparticles based on two approaches. The first approach explores the viability of molecular intervention to the assembly-disassembly-reassembly process. The temperature-induced assembly and disassembly processes of DNAs and gold nanoparticles were studied as a model system to illustrate this approach. The introduction of a molecular recognition probe leads to intervention in the assembly-disassembly process depending on its specific biorecognition. This process was detected by monitoring the change in the optical properties of gold nanoparticles and their DNA assemblies. The second approach involves the disassembly of the DNA-linked assembly of nanoparticles using restriction enzymes (e.g., MspI). The presence of the double stranded DNAs in the nanoparticle assembly was also substantiated by a Southern blot. Implications of the results to exploration of the molecular intervention for fine-tuning interfacial reactivities in DNA-based bioassays are also discussed.