Robust, rapid and sensitive detection of specific molecules at ultra low concentrations is becoming increasing important, especially for medical diagnosis, food safety and environmental protection. Various spectroscopic techniques have been developed to apply in analysis and assay fields, including fluorescent spectroscopy, infrared spectroscopy and surface-enhanced Raman spectroscopy (SERS), etc. Multiphonon resonant Raman scattering (MRRS) technique is usually used to investigate optical lattice vibrations and the interaction between phonon and electron in semiconductor nanomaterials. Recently, it exhibits fascinating prospects in biodetection due to its significant specific spectroscopic and material advantages. The multiple-order phonon lines are material intrinsic and thus can be used as a characteristic fingerprint signal to label the biomolecules. The strong anti-interference capacity to external environment allows an accurate detection. Narrow bandwidth makes the technique suitable for multiplexed analysis. Proper choice of nontoxic inorganic semiconductor materials facilitates in-vivo detection. This review focuses on the current theoretical and technical developments in MRRS of semiconductor nanomaterials and highlights their applications in bioanalysis. The basic principle, merits, challenges and future perspectives of MRRS detection technique are discussed.