Biosecurity and invasive alien species were major ecological issues of biosecurity at the national gate. Biological invasions has caused huge economic losses and rapid loss of biodiversity, and also affected human health. Tibet is an important ecological security barrier in China with complex and rich ecological types. It is of great significance to clarify the potential distribution pattern of invasive alien plants and their responses to climate change on a regional scale in Tibet for the prevention and control of invasive plants. In order to investigate the impact risk of the invasive plant Datura stramonium L. on the ecological security of Tibet, we used the Maxent model based on field survey data, applied R language and SPSS software to optimize the model parameters and data screening, explored the main environmental factors affecting its geographical distribution, and simulated and predicted its distribution in Tibet under contemporary and two climate change scenarios (RCP 45 and RCP 85) in 2050s and 2070s. We also simulated and predicted the distribution of potential invasion risk areas in Tibet under contemporary and two climate change scenarios (RCP 45 and RCP 85) in 2050s and 2070s. The results showed that: soil pH of subsoil, annual average temperature, the maximum temperature of the warmest month and available soil water content were the dominant environmental factors affecting the distribution of Datura stramonium L., and elevation and intensity of human activities also played an important role; Lang County, Jiacha County, Naidong County, Chengguan County, Basu County, Gongga County, Bayi County, Bomi County, Chayu County, and Mankang County would be the high risk areas for D. stramonium L. invasion based on field survey and model prediction; The area of risk areas at the respective levels and in the total risk area of D. stramonium L. showed trends of a continuous increase under two climatic backgrounds, and the response was more sensitive under the RCP 85 scenario (the highest carbon emission scenario); The trend of invasion and dispersal was mainly along the low elevation river valley area from southeast to northwest, and the distribution center would move from the current Medog County area to GongbuJiangda County area. To sum up, the distribution of D. stramonium L. in Tibet was greatly affected by soil environment, temperature and precipitation, and climate change and intensity of human activities will cause them to spread to western and northern Tibet. The results of the study can provide an ecological basic theoretical basis for the comprehensive prevention and control of the invasion hazard and dynamic monitoring of D. stramonium L. in Tibet.