A novel countercurrent seepage bioreactor immobilized with P. chrysosporium was stably operated for almost half a year under non-sterile conditions for the simultaneous removal of naproxen and carbamazepine from synthetic wastewater. The removal efficiency for carbamazepine was about 80% while naproxen was almost completely removed. The countercurrent seepage mode contributed to increase the white-rot fungus resistance to the bacterial contamination occurring in the bioreactor. The enzyme kinetics parameters Km and Vmax values for naproxen and carbamazepine were 10.87 mg/L and 2.50 mg/L min and 33.55 mg/L and 3.33 mg/L min, respectively.