Semiconductor and magnetic nanoparticles hold unique optical and magnetic properties, and great promises for bio-imaging and therapeutic applications. Here, we present a novel scheme of synthesizing fluorescent PbS and magnetic Fe3O4 nanoparticles (NPs) using DNA and RNA oligonucleotides with various sequences. The bonding chemistry between oligonucleotides and NPs is studied using FTIR, suggesting that the different chemical moieties of nucleobases passivate the NP surface. Strong coordination of oligonucleotides provides the chemical and colloidal stabilities, leading to high particle yields. The PbS NPs have a variable fluorescence quantum yield depending on the sequence used, and a narrower size distribution than Fe3O4 NPs. Numerical simulations confirm that the reactivity of oligonucleotides is responsible for surface capping and growth of these two types of NPs. The experimental and numerical results show that the oligonucleotide sequence plays a crucial role in creating NPs, and this capping chemistry is applicable for various types of nanocrystals. This new synthesis scheme should be valuable in interfacing inorganic NPs with biomolecules for a variety of biological applications.