Flexible pressure sensors have shown great application potential in intelligent robotics, healthcare monitoring, and human-machine interfaces. However, critical challenge exists in reconciling the trade-off between high sensitivity and wide linear sensing range. Here, inspired by the delicate microstructures of human skin, a piezoresistive pressure sensor with soft-hard synergistic interlocked (SHSI) microstructures is proposed to enhance the sensitivity while maintaining broad linear sensing range. The proposed SHSI sensor is face-to-face assembled by a soft sensing layer with spinosum microstructures and a hard interdigital electrode layer with dome microstructures. The design of SHSI microstructures enables efficient mechanical stimulus amplification and consistent compressibility of the sensor under pressure. Consequently, the as-prepared SHSI sensor simultaneously exhibits a maximum sensitivity as high as 67.1 kPa(-1) and a wide linear working range up to 650 kPa. Meanwhile, low limit of detection (7 Pa), fast response (40 ms) and recovery (37 ms), as well as prominent stability and durability over 10,000 cycles of the sensor are realized. Owing to these outstanding sensing performances, the successful applications of the SHSI sensor in physiological signal monitoring and wearable human-machine interfaces are demonstrated. This work offers a general design approach to achieve coordination of high sensitivity and broad linear range of flexible pressure sensors.