Identifying molecular biomarkers promises to significantly improve the accuracy in cancer diagnosis at its early stage. DNA nanomachines, which are designable and switchable nanostructures made of DNA, show broad potential to detect tumor biomarkers with noninvasive, inexpensive, highly sensitive, and highly specific advantages. This Feature summarizes the recent DNA nanomachine-based platforms for the early detection of cancer biomarkers, both from body fluids and in cells.