High-speed railway lines in northwestern China include densely distributed long tunnels and tunnel groups, where continuous variations in air pressure arise from altitude changes. When electric multiple units (EMUs) frequently traverse such complex tunnel environments, pressure fluctuations inside passenger compartments intensify, adversely affecting passengers′ aural comfort. In this study, based on full-scale real-train test data from the Qinling Mountains section of the Xi′an-Chengdu high-speed railway and the Baoji-Lanzhou high-speed railway, the characteristics of internal/external pressure fluctuations, pressure comfort, and airtightness efficiency of high-speed EMUs operating on different lines are systematically investigated. The results show that (1) increasing tunnel slope significantly amplifies internal pressure fluctuations, with Δp/1 s and Δp/3 s rising by 64.8% and 51.35%, respectively, under a 25‰ slope; (2) tunnel groups degrade pressure comfort both inside and outside the train, causing cumulative internal pressure reductions, although peak-to-peak pressure variations between compartments remain below 4.44% (R²> 98.61%); (3) the pressure comfort index, evaluated using UIC 660, indicates that passenger comfort in the Qinling Mountains section of the Xi′an-Chengdu high-speed railway is inferior to that of the Baoji-Lanzhou high-speed railway, with the downward direction on the same line more prone to inducing aural discomfort; and (4) the opening/closing characteristics of passenger compartment pressure protection valves vary with line environment. The average airtightness efficiency of EMUs on the Baoji-Lanzhou high-speed railway is 0.77, which is 60.4% higher than that of the Qinling Mountains section of the Xi′an-Chengdu high-speed railway.