Microstructures have been proved as crucial factors for the sensing performance of flexible pressure sensors. In this study, polypyrrole (PPy)/sunflower pollen (SFP) (P/SFP) was prepared via the in situ growth of PPy on the surface of degreased SFP with a sea urchin-like microstructure; then, these P/SFP microspheres were sprayed onto a flat silk cocoon (FSC) to prepare a sensing layer P/SFP-FSC. PPy-FSC (P-FSC) was prepared as an electrode layer through the in situ polymerization of PPy on the FSC surface. The sensing layer P/SFP-FSC was placed between two P-FSC electrode layers to assemble a P/SFP-FSC pressure sensor together with a fork finger electrode. With 6 mg/cm2 of optimized sprayed P/SFP microspheres, the prepared flexible pressure sensor has a sensitivity of up to 0.128 KPa-1 in the range of 0-13.18 KPa and up to 0.13 KPa-1 in the range of 13.18-30.65 KPa, a fast response/recovery time (90 ms/80 ms), and a minimum detection limit as low as 40 Pa. This fabricated flexible P/SFP-FSC sensor can monitor human motion and can also be used for the encrypted transmission of important information via Morse code. In conclusion, the developed flexible P/SFP-FSC pressure sensor based on microstructure modification in this study shows good application prospects in the field of human-computer interaction and wearable electronic devices.