Abstract: The nuclear fuel of medical isotope production reactor (MIPR) project will make great contribution to reactor technology R & D and application, popularization and application of new technology for the production of radionuclide drugs, development of medical radionuclide industry, and making patients with special diseases especially malignant tumors, to get better diagnosis and treatment with a lower cost. At the same time, it can help the MIPR to carry out the experimental research on the radiation performance of the special and large size shielding material and fill the blank of the country. MIPR is the reactor of uranyl nitrate (or uranyl sulfate) solution. The purpose of MIPR is to produce molybdenum-99 (⁹⁹Mo) and iodine-131 (¹³¹I). And the safety of MIPR is also the very important issue to be considered as other reactor type. Under the condition of primary cooling pump failed, or mis-withdraw rods, or gas loop hydrogen and oxygen recombiner function failed etc., emergency reactor trip system (ERTS) should be action. There are two ERTS action modes: positive pressure mode and negative pressure mode. In this article the emergency reactor trip system design principle of MIPR has been presented, and transient of emergency trip of MIPR has been analyzed on two system action modes. Calculation results show that the fuel can be completely unloaded within 150 s by positive pressure mode for emergency shutdown; and 700 s by negative pressure mode. The positive pressure mode is more advantage. Analysis results of this article can provide the input data for reactor safety analysis.