Human consumption of non-steroidal anti-inflammatory drugs (NSAIDs) is increasing, which poses a great risk of pollution by these pharmaceuticals on the aquatic environment. Therefore, this study reports the optimization of microwave-assisted extraction using water as a green solvent and hollow fiber liquid-phase microextraction (HF-LPME) methods followed by high-performance liquid chromatography-high resolution mass spectrometry analysis of NSAIDs in wastewater and aquatic plant, Eichhornia crassipes. The optimized MAE resulted in efficient transfer of selected NSAIDs from plant samples into the aqueous phase yielding the recoveries ranging from 91 to115%. A multivariate approach based on half fractional factorial and central composite design was used during the optimization of HF-LPME. Under the optimized conditions, the maximum enrichment factors for naproxen, fenoprofen, diclofenac, and ibuprofen were 49, 126, 93 and 156, respectively. The overall analytical method recoveries ranged from 86 to 116% while the limits of quantitation for wastewater and plant samples ranged from 0.09 to 0.59μgL-1 and from 0.11 to 0.59μgkg-1, respectively. The precision of the proposed analytical method which was measured in terms of RSD values did not exceed 5%. Naproxen was the most abundant compound in both wastewater and the Eichhornia crassipes plant samples with concentrations of up to 3.30μgL-1 and 10.97μgkg-1, respectively. The detection of NSAIDs in Eichhornia crassipes means this plant has the ability to bioaccumulate pharmaceutical load in surface water.