According to the United States Environmental Protection Agency, the trace organic contaminants (TrOCs) are increasingly being detected in water bodies at low concentration levels (ng/L to μg/L), but the risks they pose to human health and ecosystems are still not fully understood and they are not included in the existing water quality regulations worldwide. These contaminants consist of hormones and steroids, personal care products, pharmaceutically active compounds (PhACs), flame retardants, alkylphenols, and pesticides. Among TrOCs, PhACs are a huge and diverse group of organic compounds, including antibiotics, antiinflammatory drugs, antiepileptics, cytostatic drugs, and β-blockers. Naproxen [NPX; (S) 6-methoxy-α-methyl-2-naphthalene acetic acid] is a non-steroidal anti-inflammatory drug currently being found in aquatic environments (usually at μg/L levels) due to its excessive use to reduce pain. Many physicochemical processes have been developed to remove NPX from the artificially contaminated water but have generally shown such disadvantages as the high operational costs and the generation of secondary pollutants, compared to the biological processes. In this study, two fixed-bed reactors (working volume, 3 L each) containing the whiterot fungus (WRF) Phanerochaete chrysosporium immobilized on wood chips and operated under submerged and countercurrent-submerged modes were used to remove NPX (at 1 mg/L) from the artificially contaminated water. The reactors were operated under the intermittent feeding and continuous aeration mode to find out a strategy for a stable reactor operation under non-sterile conditions. The activity of P. chrysosporium on the NPX removal was first evaluated by batch experiments with the WRF in suspended and immobilized systems. Results showed NPX was almost completely removed (80.11±2.10%) in the immobilized system, while the fungus was not that active in the suspended system (removal efficiency at 61.75±1.65%), suggesting the immobilization strategy played a major role in enhancing the enzyme production and consequently improving the NPX bioremoval to some extent. On the other hand, NPX was almost completely removed in both reactors after 14 days even though a sharp decline in the removal efficiency ( < 20%) was observed in the submerged reactor as a result of the contamination by indigenous bacteria. To overcome this bacterial contamination, sodium hypochlorite (at 8.25%) was added into the influent (at 1:100, v/v) on day 20, followed by the NPX removal efficiency recovered accordingly. In comparison, the bacterial contamination was not observed in the countercurrent-submerged mode and the reactor operation was relatively stable during 28 days. Therefore, the countercurrent-submerged mode could be considered a viable strategy to enhance the ability of WRF to degrade the micropollutant under nonsterile conditions. This mode showed a major role in increasing the fungal resistance to the bacterial contamination, mainly due to the different flow pattern inside the bioreactor and the highly efficient transfer of oxygen and nutrients to WRF.