Large break loss of coolant accident is one of the most important design basis accidents, the accurate calculation can provide great support to enhance the plant power. In this study, the best estimate program RELAP5 is used to simulate the condition FP-LP-2 during the experiments of the loss of fluid test (LOFT), and the Gesellschaft für Anlagen-und Reaktorsicherheit (GRS) uncertainty analysis method is applied to the uncertainty quantification and sensitivity analysis. The uncertainty envelope with 95% confidence of key output parameters is given, and the uncertainty trend of these output results and their reasons are analyzed. Sensitivity analysis shows that the factors with effects on the peak cladding temperature include core decay heat, the critical flow discharge coefficient of the intact loop break, and the thermal conductivity of the fuel rod. This study confirmed the effectiveness of the GRS method, and can provide support to improve the safety analysis method.