One of the options to prevent membrane fouling is to implement air lifting that can improve the cake removal from the membrane surface. This study presents the results of tests that were carried out at the Institutes for Desert Research, Kiryat Sde-Boker, Israel, and focused on the influence of hydrodynamic conditions on fouling in a pilot-scale immersed membrane bioreactor (IMBR) using a hollow fiber membrane module of ZW-10 (Zenon Environmental, Canada) under ambient conditions. In this system, the cross-flow velocities across the membrane surface were induced by one conical and four cylindrical draft-tubes. The relationship between the crossflow velocity and the aeration intensity, the influence of the crossflow on fouling rate under various hydrodynamic conditions were investigated and optimal operating conditions were obtained. Optimal operating conditions were reached during the long-term experiment period (70 days) for the treatment of domestic wastewater. The system was stable without external chemical cleaning. The results showed that the permeate was of high quality, and the removal of COD and BOD was 94.0% and 98.8%, respectively. The crossflow near the membrane surface reveals a major contribution for minimizing membrane fouling, and could offer guidelines for future design of similar systems.