Abstract: Toxic gases released during drilling and blasting operations in underground powerhouse of hydropower stations pose a serious threat to the safety of super-large cavern construction. This study takes the Level Ⅳ main plant of Hubei Pingtan Yuan Pumped Storage Power Station for a case study to address the challenges of toxic gas removal during mixed ventilation in super-large-section underground caverns. A CFD numerical model was established for CO diffusion under an opposed arrangement of extraction and pressure ducts, which was then validated through field monitoring data. A numerical computation system was also employed to simulate the impact of the synergistic distance between extraction and pressure ducts on CO diffusion. Results indicate that as the mixed ventilation flow field stabilized in the opposed arrangement, fully developed jets synergized with extracted airflow to form distinct primary channels, enabling CO dilution and diffusion to progressively migrate from the working face toward the tunnel exterior. When the synergistic distance between extraction and pressure ducts was controlled at 30 m, a "push-pull synergy" mechanism was established rapidly, leading to improved ventilation efficiency compared to that in the 20 and 40 m scenarios. This study provides references for the parametric design and efficient operation of ventilation system in underground powerhouse of hydropower stations.