In this study, we use density functional theory (DFT) calculations to investigate the effect of moisture on the performance of three types of nanofiber (NF)-based air-filter media prepared by electrospinning polyvinyl alcohol, polyvinylidene fluoride, and polyacrylonitrile (PAN). Based on the DFT calculations of the intermolecular interactions between the NF-based filter media and water molecules, the PAN-NF filter is expected to exhibit the best performance in the wet state. Experiment studies also successfully demonstrate that the PAN-NF filter medium has better performance in the filtration of particulate matter (PM) than a commercial semi-high efficiency particulate air filter under wet conditions, and these results are in good agreement with the DFT calculation. The PAN-NF filter shows better performance because of its hydrophilic nature and the relatively low thickness the filter medium that allowed fast recovery of its PM-filtration performance.