The sensitivity of the operating parameters of proton exchange membrane fuel cells is essential to improve the performance and water management capabilities of the stack. The current research on proton exchange membrane fuel cell sensitivity is mainly focused on simulations and experimental methods for small activation area single cells, but less research literature for commercial stack with larger effective area. In this work, a commercial stack with an effective area of 300 cm2 membrane electrode is as the research object. The polarization curves under different operating conditions are obtained by experiment, and the voltage data are processed with first-order derivatives to systematically analyze the effects of gas relative humidity, stoichiometric ratio, inlet gas pressure and operating temperature on the performance of the stack. It was found that a certain degree of cathode inlet relative humidity, cathode stoichiometry ratio, in inlet pressure and in temperature are beneficial to the stack performance and are closely related to stack water management. However, with the cathode gas relative humidity reaching 45%, the cathode stoichiometry ratio increasing to 1.9 and the operating temperature increasing to 76°C, the stack performance does not improve significantly. And the excessive increase in operating parameters is likely to have a negative impact on the stack performance. The stack performance is less sensitive to the anode stoichiometry ratio and anode gas relative humidity, and when the anode stoichiometry ratio is lower than 1.3, it will have a great negative impact on the stack performance. These are important for the development of controlling the operating parameters for commercial fuel cell.