This study investigated the effects of operators’ video gaming experience and the number of unmanned aerial vehicles (UAVs) on their operations of multiple semi-autonomous UAVs for searching and rescuing tasks. Through simulation experiments, the findings revealed that operators with extensive video gaming experience, especially RTS and MOBA players, demonstrated superior task performance and less perceived mental workload. Regarding the number of UAVs, using four UAVs achieved an optimal system performance while didn’t increase workload or impair situation awareness. The results provided a theoretical foundation for the design and optimization of semi-autonomous human-robot collaboration systems and offered valuable insights for future hardware development and implementation.