The effect of total dose radiation on the single event effect of uniaxial strained Si Nano channel metal oxide semiconductor field effect transistor (NMOSFET) was studied by TCAD simulation. By comparing the experimental results, the TCAD simulation model of the 50 nm strained Si NMOS device is established. The model is used to simulate the off-state single event effect (V ds = 0.05) of NMOSFET under the total dose radiation. The results show that total dose radiation increases the body potential of NMOSFET devices and intensifies the single event transient process of NMOSFET devices. The transient current increases by 4.88% and the drain charge increases by 29.15% under the total dose of 2KGy, which indicates that the effect of total dose radiation on the single event effect is the main factor affecting the collection of drain charge. Therefore, the experimental results and the established model provide good reference for the study of irradiation reliability of the uniaxial strained Si Nano NMOSFET and the application of strained integrated circuits.