Optical micro-nanofibers (MNFs) have diameters close to or smaller than the wavelength of the guided light. Recently, MNFs have attracted wide attention due to their important applications in optofluidic sensors. This paper begins with a brief introduction of the fabrication methods and waveguiding properties of MNFs. Based on intensity and phase modulation, we introduce the research progress of optofluidic MNF sensors in chemical and biological sensing with high sensitivity, fast response, and small footprint. Finally, the development and application of optofluidic MNF sensors are summarized and prospected.