In semiconductor nanowire (NW) photodetectors, the Schottky barrier formed by the contact between metal and semiconductor can act as a depletion layer. For NW structures with a smaller diameter, the depletion region is especially important to the carrier transport. We prepared a GaAs/AlGaAs quantum well NW photodetector with a two-dimensional electron-hole tube, in which the two-dimensional hole tube (2DHT) formed by the inner layer of GaAs and AlGaAs has the most important role in the regulation of carriers. By adjusting the bias voltage to vary the depth of the depletion region, we have confirmed the influence of the depletion region in a 2DHT. A significant inflection point was found in the responsivity-voltage curve at 1.5 V. By combining the depletion region and 2DHT, the responsivity of the fabricated device was increased by 18 times to 0.199 A W-1 and the detectivity is increased by 5 times to 5.8 × 1010 Jones, compared to the pure GaAs NW photodetector. Reasonable combination of depletion layer and 2DHT was proved to promote high-performance NW photodetector.