ABSTRACTPressure sensor has become an important part of physiological condition monitoring system because it can respond to small pressure in human activities. Tissue paper has been studied as a carrier of sensitive unit layer for pressure sensors in recent years due to its internal pore structure and wrinkle morphology of surface. In this work, the pore structure of the tissue paper is improved by the principle of hydration and destruction of hydrogen bonds. Based on flexible substrate of NaOH modified tissue paper (NMTP) with enhanced pore structure, combined with dip‐coating composite conductive filler, the pressure sensor is fabricated by sandwiching the sensitive unit between the interdigital electrode and the microdome elastomer through layer‐by‐layer assembly method. Thanks to the excellent interfacial resistance effect of porous NMTP under pressure, the sensitivity of NMTP‐based pressure sensor is as high as 37.5 kPa−1 in a pressure range of 0–2 kPa. Finally, the follow‐up studies on pressure sensors have been proven to be applicable to a variety of physiological activity such as pulse detection, respiration detection and voice recognition. The NMTP‐based sensitive unit provides alternative strategy to improve performance of pressure sensors and extends potential applications in monitoring human physiological activities. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48973.