of flexible sensors, piezoresistive pressure sensors are of great interest as electronic skins, [19][20][21] wearable monitors, [22][23][24] and human-machine interfaces [25,26] for their easy signal readout and collection, simple device structure, low energy consumption, and high sensitivity. [27] For instance, remote healthcare becomes possible with the help of flexible mechanosensors, which can be directly attached to the human body enabling timely and wireless acquisition of vital physiological signals via continuously monitoring the blood pressure, heartbeat speed, and joint movement. [28,29] Moreover, pressure sensors can provide haptic feedback when combined with robotic arms, improving the reliability and efficacy of industrial production. [30] Nevertheless, the bottleneck existing in the field of pressure sensor design remains to be the trade-off between sensitivity and sensing range.Human skin, which is the largest organ of the body, possesses enormous functions of protection, excretion, temperature regulation, and perception. [7] Skin basically contains epidermis as the protective layer, dermis as a cushion layer for buffering stress/strain, mechanoceptor connected with dermis for amplifying and efficiently transferring tactile stimuli, and sweat glands for temperature regulation. [31,32] Inspired by the interlocked microstructures of epidermis and dermis, piezoresistive pressure sensor consisting of two conductive layers stacked in a face-to-face manner has been widely explored due to its large output current changes upon loading and its performance has been much enhanced by introducing High sensitivity and broad sensing range are considered as two crucial parameters toward flexible and wearable piezoresistive pressure sensors for human healthcare, human-machine interfaces, robots, and so on. Though various strategies are developed to improve the sensor performance, the trade-off between sensitivity and sensing range remains a bottleneck for device design. Besides, conventional pressure sensors without gas permeability normally cause discomfort and inflammation to the human skin. Herein, enlightened by the functions and structure of the human skin, this article proposes a stiffness engineering strategy for constructing Ti 3 C 2 T X MXene-based porous spinosum structure to boost sensitivity over a broad detection range. Consequently, the as-fabricated pressure sensor exhibits superior performance, including ultrahigh sensitivity of 367 kPa −1 over a widened detection range, a low detection limit of 1 Pa, good gas permeability, and exceptional mechanical stability over 5000 compression cycles at high pressure. Benefiting from such excellent performances, a variety of fancy applications in detecting static pressure, including physiological signals, stealth transmission, the magnitude and spatial distribution of external tactile stimuli, as well as differentiating spatiotemporal tactile stimuli, are demonstrated. It is believed that stiffness engineering is a universal strategy for tailoring the performan...