Abstract: In order to explore the temporal and spatial variation characteristics and ecological significance of human interference index (HII) in coastal areas above the county level, the HII calculation method is improved by using remote sensing data and GIS technology to make it more suitable for the calculation of large-scale research area. The spatiotemporal variation characteristics and key driving factors of HII in Jiangsu coastal zone from 1990 to 2020 were analyzed. The ecological significance of HII was discussed based on the correlation analysis results between HII and selected representative indicators eventually. The results showed that: (1) The spatial distribution of HII in cities and counties in the study area decrease initially and increase afterwards but decrease ultimately from north to south; The HII of the study area in 1990, 2000, 2010 and 2020 were 0.2800, 0.3620, 0.1804 and 0.2917; (2) The expansion of artificial buildings and tidal flat reclamation were the key driving factors affecting the spatial distribution of high-value HII in the study area; (3) The results of correlation analysis showed that the patches in the study area had experienced the process from agglomeration to fragmentation and then to agglomeration, there were some ecological significance in the method of HII. The results of this study can not only provide more spatial information and theoretical guidance for the regulation of human activities and ecosystem management in the coastal zone of Jiangsu Province, but also offer ideas for calculating the HII of large-scale space.