Developing an advanced individual protection cloth is a pivotal factor in combating global pathogen epidemics. However, formidable challenges are posed by the triangularity imbalance effect, necessitating the simultaneous fulfillment of requirements for high comfort, high safety, and mass production. In this study, a mass-producible hybrid polytetrafluoroethylene nanofiber mat (HPNFM) was developed by integrating technologies of organic–inorganic hybridization and membrane asynchronous stretching. Exceptional comfort was attained by conferring waterproofing and breathability attributes, achieved through the radial island-chain architecture exhibiting hydrophobicity and nanoporosity. Furthermore, through the incorporation of high-efficiency anti-pathogen nanoparticles, the HPNFM ensures high safety, demonstrating active antibacterial and antiviral effects. This is achieved through the synergistic effects of electrostatic induction and reactive oxygen species-based pathogen inactivation. More significantly, an HPNFM-based individual protective suit is designed and manufactured, which successfully encapsulates the advantages of high comfort, safety, and mass production, displaying competitiveness as a commercial product. Positioned as a viable strategy, this work holds substantial potential for practical applications in responding to future epidemics.