Simultaneous biodegradation of toluene and p-xylene was performed in a novel bioreactor, and the performance was analyzed on the basis of both experimental and mathematical simulation results. The novel bioreactor employed a silicon tubing as a supplier of the aromatic solvents to be treated, and the transfer rate of toluene and p-xylene into the culture broth was easily controlled. Batch, sequencing batch, and continuous mode of operation were carried out in the novel bioreactor to compare the performance of the biodegradation of solvent mixture. Sequencing batch operation worked well, but several operational difficulties were found. Continuous operation was shown to present higher biodegradation rates and operational stability. The continuous biodegradation process was mathematically simulated, and operational conditions were optimized on the basis of the simulation results.