Vegetation coverage and its response is an important topic in current global change research. Studying the temporal and spatial change trend of vegetation coverage in the Huaihe River basin is of great significance for revealing the evolution and driving mechanism of fragile ecosystems in the climate transition zone. The Landsat images on the Google Earth Engine (GEE) platform were used to calculate the fraction of vegetation coverage (FVC) of the Huaihe River basin, and the temporal and spatial change characteristics of FVC were analyzed. The driving factors of FVC were analyzed from interannual and spatial scales with the data of night light, temperature, precipitation, evapotranspiration, soil and topography. The results showed that from 1987 to 2021，the overall FVC in the Huaihe River basin showed an increasing trend. The change trend of FVC was mainly stable and improved in space, accounting for 45.2% and 39.7%, respectively. The improvement area was concentrated in Xinyang, Zhumadian, Nanyang, Luoyang, etc., while the degradation area was mainly found in Nantong, Taizhou, Yancheng, Linyi, Weifang, Zhengzhou, Fuyang, etc. On the interannual scale, the correlation between FVC change and night light data was higher than that of temperature and precipitation, and the increasing trend of FVC in Huaibei was not as significant as that in Huainan. On the spatial scale, nighttime light, potential evapotranspiration, precipitation and terrain were the main factors affecting the spatial differences of FVC in the Huaihe River basin, and human activities represented by nighttime light had the greatest impact on FVC. The influence of nighttime lighting data on FVC change had spatial heterogeneity: the area of positive correlation area accounted for 25.4%, mainly cultivated land and forest land. The area of negatively correlated areas accounted for 14.7%, mainly distributed in the central urban areas of prefecture-level cities and even counties. The joint effect of human activities and natural factors was the main cause of vegetation change in Huaihe River basin in the past 35 years. The average contribution of human activities and natural factors to FVC change was 56.0% and 44.0%, respectively. The research results can provide support for the formulation of green urbanization road and ecological protection policy in China.