Purpose: Centrifugal pumps are prone to vibration problems during operation due to poor dynamic characteristics of its impellers that serve as the only running parts of such devices; the dynamic characteristics of the impeller during operation are the main reasons for the vibration of the centrifugal pump. Therefore, it is important to study the internal fluid flow and its influence on the dynamic characteristics of the pump impeller and to explore the causes of vibration during the transient start-up process. The understanding of such phenomena may lead to better design of such impellers. Methods: The geometry of the flow channel inside the centrifugal pump is established using Creo 4.0 software (American PTC company). The internal fluid flow computer simulation is carried out using Flomaster V9 software (UK Flowmaster company) to obtain the variation law of speed and flow during the start-up of the centrifugal pump, which is loaded into the simulation calculation of the centrifugal pump. The variation of speed and flow during the start-up process was further processed using the fluid-structure coupling method, and the structural vibration characteristics of the impeller under transient radial force are obtained by harmonic response analysis. Results: During the starting process of the centrifugal pump, the speed and flow first increased sharply and then decreased until reaching a stable process. During this period, the impeller vibration changed sharply; the overall vibration amplitude increased and fluctuated stably at the amplitude of 0.01 mm. In the unsteady numerical simulation of the centrifugal pump, the radial force on the impeller changes periodically. The time domain signal is transformed into a frequency domain signal, and the fundamental frequency of the impeller and the passing frequency of the blade are 101.67 Hz and 610 Hz, respectively. Conclusions: The radial force is the main cause of impeller vibration, and the transient radial force has the least dynamic impact on the impeller structure under the design condition and has a relatively large impact under the off-design condition. In order to ensure the stable operation of the centrifugal pump, it is necessary to avoid the centrifugal pump working under the non-standard flow condition, especially the small flow condition.