This paper presents oxygen excess ratio (OER) control methods for proton exchange membrane fuel cell systems based on high-order sliding mode (HOSM) observer. The non-linear and strong coupling characteristics make it difficult for the nonlinear uncertain systems to realize OER closed-loop feedback control. An improved HOSM observer is developed to observe the unmeasurable system states. Even under the interference of model parametric uncertainties, external disturbances, and measurement noises, the HOSM observer can still show fast convergence and good robustness. With the output error injection feature of improved HOSM algorithm, OER can be reconstructed in finite time. The proposed two stage sliding mode based on super twisting algorithm plus feedforward (TS_SM_STW+FF) controller and TS_SM_STW plus fuzzy feedforward (TS_SM_STW+Fuzzy_FF) controller are applied to regulate the estimated OER to track optimal value, respectively. The dynamic performance of OER with proposed methods is validated through the RT-LAB hardware-in-loop platform. The experimental results have shown the feasibility and effectiveness of proposed controllers as compared with conventional strategies.