The particulate air contaminations, including particulate matters (PMs) and dangerous bioaerosols, cause adverse impact on public and thereby has prompted the development of air filtration systems. Although numerous membrane-based air filters can achieve promising filtration effects, they still suffer from decreased efficiency and short service life due to their instable surface attractive sites (e.g., electrostatic charges) and surface fouling/clogging problems. Here we show a functional liquid-mediated filtration system (LMS) constructed over fibrous matrix to overcome the conventional limitations, achieving an overall optimal filtration performance. The functional liquid layer with high surface tension and adequate liquid viscosity (e.g., glycerol) can strongly attract and adhere the contaminated particles at the interface, and ultimately retain them inside the liquid layer. Significantly, owing to the high stability of the liquid cladding over fiber matrix, the LMS displays an overall long-lasting efficiency and robustness (filtration efficiency reaching over 99% for 3 months usage without resistance increase) and its dust-holding capacity can achieve 100 g·m2 with no change on pressure drop, outperforming most of the commercial facepiece filters. Moreover, the LMS builds a defense line to the spread of respiratory diseases by efficiently filtering tiny-sized dangerous bioaerosols, such as fatal viruses and bacteria, realizing the virus (SARS-CoV-2, BetaCoV) concentration degradation for 3 orders of magnitude. The system is also resistant to the common fouling and clogging issues as the liquid filtering layer can be adjusted and regenerated to maintain its prominent functions. This work paves the way for solving the present air filtration challenges within the membrane-based filtration systems and contributes to the improvement of air purification technologies for environment and healthcare.