Large centrifugal pumps can generate electricity in reverse, reducing the power supply pressure of the power grid. However, S region may occurs during the operation and regulation of the pump as a steam turbine (PAT). The S region can cause unstable unit startup, not only causing hydraulic system oscillation, but also accompanied by strong vibration and noise. Understanding the characteristic curve of the S region is of great significance for improving unit stability and efficiency. Previously, the main research object in S area was small generator units. This article conducted unsteady numerical simulation and experimental research on a large centrifugal pump. Analysed the internal flow rate, blade load, entropy generation, and pressure pulsation under three special operating conditions: the optimal operating condition, runaway operating condition, and braking operating condition in the S region. In addition, a comparative analysis was conducted on three pairs of operating conditions: S region turbine mode and reverse pump mode, with opposite flow direction, similar flow rate, and the same speed. Research has found that in the S region of large centrifugal pumps, the flow chaos in the turbine mode mainly occurs in the impeller section, and the maximum pressure occurs in the stationary blade section. The flow chaos under reverse pump operation mainly occurs in the stationary blade section, and the maximum pressure occurs in the impeller section.