This paper describes a flexible pressure sensor based on polypyrrole(PPy)-Cotton composites, in which PPy is grown on cellulose fibers of cotton pads via an in situ vapor growth method, which is beneficial to the homogeneity of the composites. The resulting devices exhibits rapid response and recovery speed, the response and recovery times are 220 ms and 240 ms, respectively. The optimal PPy-Cotton Pads (PCPs) sensor shows low detection limit, which is about 50 Pa. At the same time, it exhibits excellent durability in the measurement of repeated loading-unloading pressure over 1000 cycles. The resultant sensor can be attached on different positions of body and applied to recording physiological signals, such as wrist pulse, vocal cord vibration, respiration and eyes blinking. Finally, a 4 × 4 pressure sensor array shows that the PCPs sensor has capability in pressure distribution detection and represents great potential in the fields of wearable electronics and biomedical devices.