We report the use of a liquid-filled hollow-core photonic crystal fiber (PCF) as a highly controlled photochemical reactor. Hollow-core PCFs have several major advantages over conventional sample cells: the sample volume per optical path length is very small (2.8 nL cm−1 in the fiber used), long optical path lengths are possible as a result of very low intrinsic waveguide loss, and furthermore the light travels in a diffractionless single mode with a constant transverse intensity profile. As a proof of principle, the (very low) quantum yield of the photochemical conversion of vitamin B12, cyanocobalamin (CNCbl) to hydroxocobalamin ([H2OCbl]+) in aqueous solution was measured for several pH values from 2.5 to 7.5. The dynamics of the actively induced reaction were monitored in real-time by broadband absorption spectroscopy. The PCF nanoreactor required ten thousand times less sample volume compared to conventional techniques. Furthermore, the enhanced sensitivity and optical pump intensity implied that even systems with very small quantum yields can be measured very quickly—in our experiments one thousand times faster than in a conventional cuvette.