Abstract: Urbanization and economic development had resulted in an excessive human activity intensity, and regional ecological structural imbalances and deterioration. To achieve regional sustainable development and ecological restoration, it is essential to optimize natural resources utilization and control the human activity intensity of land surface (HAILS). To achieve regional sustainable development for improving ecological environment quality, we investigated the dynamic evolutionary characteristics of human activity intensity of the Yellow River Basin over the past 20 years using the construction land equivalent method, PLUS model and spatial autocorrelation analysis. The findings are as follows: (1) From 2000 to 2020, Grass Land, Cultivated Land and Wood Land were increased significantly for 4.39×105 km2, 2.83×105 km2 and 2.63×105 km2, respectively. In the future, land use types area was also showed increased trend. However, the growth rates of different land use were decreased. The spatial distribution of land use was Grass Land in the west, Cultivated Land in the middle, Wood Land besides Cultivated Land and Construction Land in the east. Unused Land was mainly concentrated on the north west part of the Yellow River Basin. (2) Human activity intensity in the Yellow River Basin increased to 12.46% from 2000 to 2050, which spatial distribution pattern showed high in the east and low in west of different provinces. During the study time, Human activity intensity in Shandong province and Henan were the highest and changed the most significantly. (3) Global spatial autocorrelation results showed: during 2000 to 2050, Moran’s I index was decreased from 0.56 to 0.17, indicating the weaken spatial dependence and the unstable spatial agglomeration. Hot spot area was mainly distributed on the Shandong province, and the cold spot area was concentrated on the southwest and middle area of the Yellow River Basin. (4) Geo-detector results indicate significant changes in the impact of various factors on human activity intensity. The explanatory power of GDP, a measure of economic growth, rose from 0.194 to 0.313, reflecting an enhanced impact. Similarly, the per capita construction land area’s influence increased dramatically from 0.345 to 0.799. Urbanization rate’s explanatory power also showed a steady increase from 0.207 to 0.323, highlighting the growing role of urbanization. In terms of industrial structure, the tertiary sector’s impact grew, while that of the primary and secondary sectors declined.