Display omitted •Low-pressure-oxygen plasma was introduced to the preparation of conductive foams.•Skeleton of plasma-treated foams have better affinity with conductive layer.•The as-prepared foams exhibit excellent compressive sensitivity and durability. Rapid development of artificial intelligence and wearable electronics facilitate the demand for high performance piezoresistive sensors. Not only high sensitivity but also good mechanical property as well as long-term usage are critical parameters to value piezoresistive sensors performance. In this work, a flexible, highly sensitive and versatile piezoresistive sensor with 3D porous structures, based on commercially available polyurethane (PU) foams coated with cellulose nanofiber @ carbon black (CNF@CB) conductive layer, was fabricated. We are particularly interested in the effect of interaction between the conductive filler and PU foam on the sensor performance. Thus, low-pressure oxygen plasma treatment was innovatively adopted to modify and activate PU scaffold to enhance the affinity between PU framework and CNF@CB conductive layer. Strong interfacial interaction is not only contributed to the sensitivity but also to the mechanical reinforcement of conductive foams, which is helpful to the long-term usage. The as-prepared PU/CNF@CB conductive foams exhibit very high compressive sensitivity of 0.35 kPa−1 (about 100% increase compared with the untreated ones), along with good mechanical property (29 kPa at 50% compressive strain, about 27% increase compared with the untreated ones) and electrical property (0.047 S/m). In addition, good stability and durability are demonstrated for the prepared PU/CNF@CB conductive foams especially under micro-pressure or micro-strain which is a huge challenge for bulk piezoresistive sensors. Such a kind of sensitive material combined with low-cost, flexibility, high sensitivity, duration, is very attractive in high-tech area.