The accurate quantification and spatial evaluation of human activity intensity is highly significant for determining the resource and environment carrying capacities of coastal areas. A human interference index (HII) was established in our study based on the minimum and maximum influences of exploitation types, the different ecological conditions within the same exploitation type and the buffer effect of exploitation on adjacent areas. It was characterized by the comprehensive consideration of the ecological features and their spatial heterogeneity. To validate the accuracy and applicability of HII, the Yellow River Delta was selected as the study area, with the years of 1987, 1995, 2005 and 2016 as the temporal scope. Then, to clarify the ecological significance of HII, the relationships of landscape pattern, vegetation net primary productivity (NPP) and soil property with HII were analyzed. The HII of the study area exhibited a continuous increase and spatial heterogeneities from 1987 to 2016. The proportion of the little interference zone kept on decreasing, the proportions of the intermediate, severe and very severe interference zones continued increasing, and the proportion of the mild interference zone initially increased and then slightly decreased. Human interference spread continuously and has been the main driving factor of ecosystem change. The HII is significantly positively correlated with patch density, edge density, and soil salinity, and negatively correlated with NPP and soil moisture content. The HII was proven to possess high accuracy, good applicability and considerable ecological significance. Therefore, it can be widely used in the evaluation of human activity intensity in coastal areas.