Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.