An accidental discharge of nitrobenzene happened in November 2005 in the Songhuajiang River, China. The AQUATOX model was modified and adapted to simulate the time-dependent nitrobenzene distribution in this multimedia aquatic system and its potential ecological impacts. Nitrobenzene concentrations in flowing water, sediment, and biota were predicted. Based on the initial concentrations of nitrobenzene observed on the field during the accidental discharge, that is, 0.167-1.47 mg/L at different river segments, the predicted water concentrations of nitrobenzene would decrease to 0.02 and 0.002 mg/L after twenty days and one month, respectively. Both model prediction and field observation were in good agreement. The predicted nitrobenzene concentrations in sediments and aquatic organisms would be lower than 0.025 and 0.002 mg/kg, respectively, after two months. Among environmental factors affecting nitrobenzene concentrations in water, inflow water dilution, water temperature, and initial concentration were the most important, by sensitivity analysis. Comparing the perturbed simulation and control simulation, the biomass changes for diatoms and mussel were significantly affected, whereas, no influence on other organisms could be predicted. Therefore the results indicated that nitrobenzene pollution in the Songhuajiang River should have a limited impact on the benthos community.