A thin film of poly(o-aminophenol), POAP, has been used as a sensor for various types of toxic and nontoxic gases: a gateway between the digital and physical worlds. We have carried out a systematic mechanistic investigation of POAP as a humidity sensor; how does it sense different gases? POAP has several convenient features such as flexibility, transparency, and suitability for large-scale manufacturing. With an appropriate theoretical method, molecular oligomers of POAP, NH and O functional groups and the perpendicular side of the polymeric body, are considered as attacking sites for humidity sensing. It is found that the NH position of the polymer acts as an electrophilic center: able to accept electronic cloud density and energetically more favorable compared to the O site. The O site acts as a nucleophilic center and donates electronic cloud density toward H2Ovap. In conclusion, only these two sites are involved in the sensing process which leads to strong intermolecular hydrogen bonding, having a 1.96 Å bond distance and ΔE ∼ -35 kcal mol-1. The results suggest that the sensitivity of the sensor improved with the oxidization state of POAP.