Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) has placed enormous diagnostic burden on hospitals and testing laboratories. It is thus critical for such facilities to optimize the diagnostic process to enable maximum testing on minimum resources. The current standard of diagnosis is the detection of the viral nucleic acid in clinical specimens. Methods: In order to optimize the laboratory’s nucleic acid testing system for COVID-19, we performed a Discrete-Event-Simulation using the Arena Simulation Software to model the detection process based on the data obtained from the First Affiliated Hospital of Guangzhou Medical University (FAHGMU). The maximum of total time that specimens spent and the equipment consumption was compared under different scenarios in the model. Results: Seven scenarios were performed to simulate actual situation and improved situations. We analyzed conditions that adding a new nucleic acid extraction system (NAES), shifting a member from night duty to morning duty, using specimen tubes containing guanidine isothiocyanate (GITC), then tested the maximum testing capacity in the current number of technicians. In addition, the costs including personal protective equipment (PPE) and testing kits was calculated. Conclusions: A work schedule based on specimen-load improves efficiency without incurring additional costs, while using the specimen tubes containing GITC could reduce testing time by 30 min. In contrast, adding new NAESs or polymerase chain reaction (PCR) instruments has minimal impact on testing efficiency.