The high-pressure SCR system is suitable for low-speed marine engines that burn high-sulfur fuel, but it will cause the increase of the exhaust back pressure of main engine, which will affect the main engine’s performance and fuel consumption. At the same time, due to the large weight and size of the SCR reactor, the overall heat storage performance of the SCR reactor is large, which makes the temperature difference between the front and back of the turbine in the start-up and shutdown of the main engine and transient conditions, affecting the transient response performance of the turbine. In this paper, 6S46ME marine low-speed diesel engine and its high-pressure SCR system are taken as the research object, the co-simulation model is constructed by using GT-Suite coupled with a programming software, and the accuracy of the test model is verified. The influence of high-pressure SCR system on the performance of main engine is analyzed, and it finds that the fuel consumption of the main engine at low load increases significantly greater than that at high load, and the exhaust temperature of the main engine changes differently at different loads. On this basis, the co-simulation model was used to analyze the matching performance of high-pressure SCR system under the transient conditions such as the main engine Tier II/Tier III mode switching process, fast-loading, normal-loading and fast-unloading. The results show that the slow cut-in/cut-out of SCR reactor is beneficial to the stable operation of the main engine system, and the cut-in/cut-out time of high-pressure SCR system greatly affects the transient fuel consumption of the main engine, and the maximum increase of fuel consumption is about 3.6 g/kW·h; In addition, the thermal inertia of the reactor has a greater impact on the performance of the main engine at low load, but not at high load.