Core-shell polyaniline/polyacrylonitrile nanofibers mat (PANI/Pan NFsM) was prepared for extraction of hydrophilic non-steroidal anti-inflammatory drugs (NSAIDs) in environmental water. Superior adsorption and desorption performance of PANI/Pan NFsM was confirmed by both static and dynamic adsorption/desorption experiments. These properties proved PANI/Pan NFsM was a potentially efficient and fast solid phase extraction (SPE) adsorbent for NSAIDs. Under the optimized conditions, only 3 mg of PANI/Pan NFsM could easily extract eight target analytes in 10 mL of water sample without any pre-treatment, and the analytes retained on NFsM could be easily eluted by 500 mu L of 1% acetic acid methanol for direct UPLC-MS/MS analysis. In addition, each piece of PANI/Pan NFsM could be reused for at least 20 times without performance decline. Possible adsorption mechanisms were also proposed. Practical feasibility was validated through the actual sample analysis.