The microstructure plays an important role in improving the sensing performance of pressure sensor.However, the design of microstructural active layer of pressure sensor usually involves complex process and expensive raw materials. Herein, the common polyester conductive electrodes and cellulose paper that both have inherent microstructure surface are ingeniously combined to form two-sided microstructure interfaces for low-cost, eco-friendly and high-performance exible piezoresistive pressure sensor. In order to obtain conductive and low-cost active layer paper, daily carbon ink, which is usually used for writing, is preferred as a conductive material. Meanwhile, we experimentally con rm that the proposed structure is also suitable for other conductive materials, such as carbon nanotubes. The results show that as-fabricated piezoresistive sensor has high pressure sensitivities of 5.54 and 1.61 kPa −1 in the wide linear ranges of 0.5−5 and 5−60 kPa, respectively, and good durability (5000 cycles under 2 kPa). The sensing mechanism of the piezoresistive sensor is analyzed by combining the characterization results and nite element simulation. Bene tting from the high sensing performance, the good exibility and non-toxic property, the piezoresistive sensor is demonstrated for multiple wearable applications (e.g., wrist pulse, speech recognition, nger bending, abdominal respiration, counting steps, and pressure distribution). This work provides a simple and universal strategy for the design of piezoresistive sensor from the microstructure interfaces between electrodes and active layer.