Flexible　electronics　have　attracted　great　interest　because　of　their　potential　applications　in　healthcare　monitoring　and　human-computer　interaction.　The　performance　of　flexible　electronics　depends　on　the　design　of　structure,　materials,　and　mechanical　responses.　In　this　work,　we　explore　the　use　of　polyurethane　(PU)　sponge　as　the　scaffold　to　form　flexible　piezoresistive　pressure　sensors　with　conductive　networks　made　from　conductive　polymer　PEDOT:PSS　and　MXene　nanosheets.　The　sensitivity　of　the　prepared　pressure　sensors　reaches　0.2171　kPa−1　under　mechanical　pressure　in　a　range　of　1.8–6.15　kPa.　The　prepared　pressure　sensors　are　re-usable　after　washing.　The　applications　of　the　prepared　pressure　sensors　in　the　sensing　of　physiological　behavior　are　demonstrated　under　the　action　of　finger　tapping,　finger　bending,　vocal　cord　vibration,　swallowing,　and　pulsing　of　radial　artery.　The　prepared　pressure　sensors　have　great　prospects　for　applications　in　human-machine　interaction　and　physiological　diagnosis.　©　2024　Elsevier　B.V.