Novel sensitive disposable sensors have been introduced for potentiometric determination of naproxen (NAP) based on single‐walled carbon nanotubes‐polyvinyl chloride (SWNTs‐PVC) composite incorporated of calix4arene as host‐guest molecular recognition element. The electrode matrix composition was optimized on the basis of the nature and content of the sensing element, cationic sites, plasticizer and nanomaterial. Remarkable selectivity and sensitivity towards NAP was achieved in the concentration range from 10−8 to 10−2 mol L−1 with anionic Nernstian compliance −61.0±0.0 mV decade−1. Modification with calixarene and carbon nanotubes improved the sensors performance through formation of NAP‐calixarene inclusion complex and promotion of the electron‐transfer processes which enhance the potential stability, response time, and shelf lifetime of the sensor. The proposed sensors were successfully applied for the potentiometric assay of NAP in dosage formulation and biological fluids under batch and flow injection analysis (FIA) conditions with average recoveries agreeable with the reported official methods.