Flexible wearable sensors, as a new generation of artificial intelligence devices, have shown great potential for applications in fields such as human health monitoring, human-computer interaction, and artificial intelligence due to their outstanding performance. However, the rapid development of pressure sensors with high compressibility and sensitivity remains a significant challenge. In this study, we successfully polymerize polypyrrole conductive particles on a polyurethane sponge substrate using a one-step method. A highly compressible sponge is prepared economically and efficiently, and a flexible pressure sensor has been successfully assembled. Due to the three-dimensional porous structure of the polyurethane sponge, it exhibits a high sensitivity response (range of pressure≤1.3 kPa, sensitivity=98.73 kPa-1) and good reproducibility (>2000 compression cycles) under applied pressure. Due to its excellent performance response, the sensors can be placed in different parts of the human body for practical monitoring of physiological and motion signals. In addition, a 5×5 pixel sensing array was prepared for spatial position and pressure analysis, demonstrating the feasibility of sensors in monitoring personal physiological parameters and human-machine interfaces.