Development of high-performance biosensors vastly facilitates the analysis and detection of various biological species, including nucleic acids, protein, cell, etc. Functional nanomaterials (e.g., silver/gold nanoparticles, carbon nanotubes, graphene, silicon nanowires, etc) serve as new platform for design of nano-biosensors featuring high sensitivity and specificity. Taking advantage of the attractive merits of silicon nanowires (SiNWs) (e.g., unique electronic/optical properties, huge surface-to-volume rations, surface tailorability, fast response and good reproducibility, and compatibility with conventional silicon technology), SiNWs have been widely employed for constructing various kinds of electrochemical and optical biosensors, enabling ultrasensitive, specific, and reproducible detection of DNA and protein. We introduce a number of typical SiNWs-based biosensors (e.g., field-effect transistor (FET), amperometric-, surface-enhanced Raman scattering (SERS), and fluorescence-based biosensors) in this chapter, aiming to summarize the representative progresses of this research field in recent years. These kinds of high-quality silicon-based sensors show potentially great promise for myriad practical applications, such as medical diagnosis, food safety, drug security, environment monitoring, as well as anti-bioterrorism and so forth.Keywords Silicon nanowires Á Biosensor Á Field effect transistor Á Surfaceenhanced Raman scattering (SERS) Á DNA and protein detection Á Sensitivity and specificity Biological/chemical analysis and detection are of essential importance for disease diagnosis, drug discovery, food safety, environmental protection, and anti-bioterrorism, etc. While a large number of bioassay kits have been available on the market, there are ever-growing efforts to develop new detection methods with ultrahigh sensitivity and specificity, to meet the increasing demands of biosensing applications. Parallel to research efforts devoted to such high-end requirements, much recent interest has been directed toward the development of low-cost and portable biosensors, which possess comparable high sensitivity to conventional instruments, but with greatly reduced cost/mass/power requirements. Nanostructures (e.g., nanoparticles [1][2][3][4][5][6][7][8][9], nanotubes [10][11][12][13][14], and nanowires [15][16][17][18], etc) Y.