Sensing nano-objects, from nanoparticles to molecules, has become a crucial need in environmental monitoring, medical diagnostics, and drug development. Detection of single particles and molecules is highly desirable, as it provides specific information on size, dynamics, and interactions. Current nanophotonic implementations rely on complex optical readout schemes, limiting their application in the field. Here we demonstrate a nanophotonic fiber-tip sensor with a compact sensor footprint and a simple readout scheme. We leverage advanced design methods to simultaneously achieve a small mode volume V m =0.74(λ/n)3, narrow linewidth Δλ=0.4nm, and a large modulation ΔR≈20% in reflection from the fiber. This unique combination of properties opens the way to sensing weak nanoscale perturbations in the vicinity of the fiber tip. In particular, we experimentally demonstrate the real-time detection of single 50 nm nanoparticles. This opens a route towards real-time sensing of single nanoparticles, and potentially single molecules, in environmental monitoring and diagnostics.