Probe reactivity has long been considered to play a key role in artificial nanochannel sensors, but systematic studies of membrane wettability on detection performance are currently lacking. Inspired by biological aquaporins, we developed an effective strategy to regulate the hydrophilic/hydrophobic balance by the controllable in situ assembly of coordination polymers (CPs) using BDC-NH2 on anodic aluminum oxide (AAO) nanochannels to promote HCHO detection. We found that the hydrophobic/hydrophilic balance in CP/AAO heterosomes plays significant roles in the effective detection of HCHO. The hydrophobic AAO barrier layer is necessary to support the confinement effect, while the hydrophilic CP surface is favorable for HCHO to access the channels and then condense with the responsive amine to generate a new imine. The optimized CP/AAO Janus device shows excellent performance in the quantitative analysis of HCHO over a wide range from 100 pM to 1 mM by monitoring the rectified ionic current.