Pressure difference inside the Polymer Electrolyte Membrane Fuel Cells (PEMFC) arises due to load variations, during which the pressure difference between anode and cathode rises. Practically, this problem can be avoided by equalizing anode and cathode pressures, to protect the fuel cell from permanent damage. This paper focuses on pressure regulation in the anode and cathode sides of the PEMFC. The control objective is achieved using second order sliding mode multi-input multi-output (MIMO) controller based on “Twisting algorithm”. Parametric uncertainty is formally presented and included in a nonlinear dynamic fuel cell model. The resultant nonlinear controller is robust and is proved to guarantee performance around any equilibrium point and under parametric uncertainty. Simulation results show that the proposed controller has a good transient response under load variations.