The emergence of multi-responsive flexible devices signifies a revolutionary era in human-machine interfaces, aiming for more realistic and diverse interaction modes. This paper develops an ultra-sensitive polyurethane (TPU) / multi-walled carbon nanotube (MWCNT) electronic skin (e-skin) which can precisely detect both pressure, strain, or their combinations at different levels in real time without signal overlap. The proposed e-skin integrates a flexible, biomimetic PDMS microcone structure with a cracked TPU/MWCNT conductive network, exhibiting exceptional sensitivity by a positive resistance response to strain (350, 70%) and a negative resistance response to pressure (–0.14004 kPa-1, 0 ~5 kPa), as well as a wide pressure detection range (100 kPa) and strain detection range (70%). Furthermore, the e-skin's durability was confirmed through repeated mechanical loading cycles (>10,000 cycles), highlighting its potential for long-term wearable applications. Extensive tests have confirmed that the proposed e-skin is capable of accurately distinguishing a series of precise physiological signals and joint movements such as pulse, heartbeat, breathing, blink and maintain reliable performance among multiple activities including bending, stretching, and pressing. This research contributes to the growing field of wearable electronics by providing a robust, skin-friendly interface capable of enhancing the efficiency and diversity of human-machine communication.