For most turboprop transport and passenger airplanes, the engine nacelle is connected directly to the lower surface of the wing, which causes unfavorable effects on the aerodynamic performance of the airplane. Through numerical simulations, the influence of a wing-mounted engine nacelle on the high-lift performance of a typical twin-engine turboprop regional airliner is investigated. Compared with a clean wing situation, a wing-mounted engine nacelle reduces the maximum lift coefficient of the landing configuration by 0.24 and makes the stall characteristic steeper. The mechanism that causes such loss of performance is mainly four unfavorable effects, which coupled act on the high-lift system. Reducing the installation height of the engine nacelle can partly recover the performance loss, but also brings significant penalty for cruise efficiency. By modifying the intersection area, the lift performance of the high-lift configuration can be raised to almost the same level, but the drag performance of the cruise configuration is not substantially deteriorated.