This paper proposes a neuro-sliding mode multivariable control approach for the control of a powered wheelchair system. In the first stage, a systematic decoupling technique is applied to the wheelchair system in order to reduce the multivariable control problem into two independent scalar control problems. Then two Neuro-Sliding Mode Controllers (NSMCs) are designed for these independent subsystems to guarantee system robustness under model uncertainties and unknown external disturbances. Both off-line and on-line trainings are involved in the second stage. Real-time experimental results confirm that robust performance for this multivariable wheelchair control system under model uncertainties and unknown external disturbances can indeed be achieved.