This study aims to enhance the removal performances of pharmaceutically active compounds (PhACs) through white-rot fungus (WRF) reactor under non-sterile conditions during long-term operation. Two chemically different PhACs namely naproxen and carbamazepine are selected for the investigation. Firstly, the study explores the possibility of WRF Phanerochaete chrysosporium, immobilized in wooden chips, to remove two target PhACs under non-sterile conditions. The removal efficiencies for both compounds in artificially contaminated water were improved by 4% for naproxen and 30% for carbamazepine in seven days, compared with the results without wooden chips. Although adsorption was crucial at the early stage, the subsequent bioremoval was found to be the main removal mechanism in the removal of both compounds. Based on the batch experimental results, a Countercurrent Seepage Bioreactor immobilized with P. chrysosporium on wooden chips was continuously operated under non-sterile conditions to treat a synthetic wastewater spiked with naproxen and carbamazepine (1,000 µg/L each) for 165 days. Naproxen was always removed to the undetectable level regardless of the experimental conditions, while the average removal efficiency for carbamazepine, a well-known recalcitrant pharmaceutically active compound, reached around 80%. The excellent removal performances are mainly attributed to the application of countercurrent seepage mode and the cardhouse fabric of the carriers, which provide the high efficiency in the immigration of oxygen and the nutrients inside the bioreactor. Combined with fungus immobilization and the temperature adjustment, the fungus activity and enzyme production were protected as well as the bacteria contamination inside the reactor was suppressed effectively. iii Besides, a prototype bioreactor namely Rotating Suspension Cartridge Reactor immobilized with P. chrysosporium was also established to treat synthetic wastewater containing 1,000 µg/L carbamazepine under non-sterile conditions. After one month of fungal adaptation, the removal efficiency exceeded 90% through such strategies as the immobilization of P. chrysosporium on the polyurethane foam cubes, the pattern of liquid/air flow inside the rotating cartridge created through the application of intermittent operational mode, and the addition of external carbon source in the influent. Both nutrient and oxygen were effectively transferred to fungi, which contributed to the excellent bioreactor treatment performance for 160-day continuous operation.