This paper summarizes our work on DNA-based nanofabrication. In the past decade, our group has developed several strategies to employ unmodified DNA nanostructures as templates for high-resolution patterning. We showed that DNA nanostructures can locally modulate vapor phase etching and deposition reactions. As a result, both negative-tone and positive-tone pattern transfers were achieved within one reaction system by adjusting reaction conditions. We also showed that DNA nanostructures can be directly imprinted onto a variety of substrates, including soft polymers and selfassembled monolayer molecules. In these cases, various surface patterns were obtained with the size ranging from micrometer to sub-10 nm. These DNA-patterned substrates have interesting interfacial properties, such as site-specific reactivity and antifouling. Overall, our work highlighted the potentials of DNA-based nanofabrication for high-resolution patterning in electronic and surface engineering applications.