Abstract: Land use and cover change are closely linked to hydrological characteristics in the basins, which greatly affects the rainfall-runoff processes, such as altering the runoff generation and the water flow pathways. Dramatic changes have taken place in land use patterns characterized by the persistent expansion of impervious surface and a continuous decrease in natural-based land cover for the most of watersheds in China under a rapid urbanization since 1980s, especially for those urbanizing or urbanized catchments. Thus, it is very important to quantify the possible effects of land use changes on hydrological processes and explore the response mechanisms of flood characteristics to the land use changes, which is also vital for land use planning, water resources management and a high-quality development in the catchment scale. Therefore, the Qinhuai River Basin, a typical semi-humid and urbanizing catchment located in the lower of the Yangtze River basin in eastern China, was selected to investigate the hydrological responses to land use changes with the historical hydrological data and land-use data. Firstly, this study quantitatively analyzed the land use changes during four periods from 2005 to 2020 and conducted a detailed analysis of the degree of transformation of different land use types and their spatial changes. The changes in some hydrological parameters caused by land use changes were estimated, and their impacts on flood processes was analyzed. Furthermore, the 18 flood events from 2003 to 2020 were selected, and the flood levels were classified based on the flood volume-peak relationship. Based on the HEC-HMS platform, a hydrological model system for the Qinhuai River Basin was constructed to analyze the response of runoff processes of different magnitude flood events to land use changes. The results showed that: (1) The area of impervious surfaces in the basin increased by 99.53%, while the area of farmland decreased by 6.57%. The increase in impermeable surfaces mainly came from the conversion of farmland, accounting for approximately 96.42%. (2) The simulation results of flood processes in the Qinhuai River Basin showed that the HEC-HMS model had good applicability, with relative errors of peak flow and flood volume during the calibration period at −1.63% , −11.79% , Nash-Sutcliffe coefficient of 0.854 , and root mean square error (RMSE) of 159.73 m³/s; and with relative errors of peak flow and flood volume during the verification period at −1.30%, 1.58%, Nash-Sutcliffe coefficient of 0.856, root mean square error (RMSE) of 133.91 m³/s. (3) The increase in impervious surfaces caused by land use changes resulted in an increase in the average curve number (CN) from 79.6 in 2005 to 80.2 in 2020, while the peak lag time significantly decreased from 1188.2 min in 2005 to 835.04 min in 2020, leading to a trend of "tall and thin" in the flood process line and an overall advance in peak occurrence time. (4) With the increase in impermeability rate under the background of urbanization, both flood volume and peak flow increased, and the impact of increasing impermeability rate was most significant for small-scale floods. Based on the analysis, the following conclusions can be drawn: (1) From 2005 to 2020, urban flooding has become the main flood disaster in the Qinhuai River Basin. Due to urban development, impermeable surfaces have expanded significantly in the southern and northern parts of the basin. (2) Land use changes have significantly affected hydrological parameters in the watershed, influencing water circulation processes and altering the runoff generation mechanism in the watershed, which further leads to significant changes in flood processes. (3) Different scales of floods respond differently to land use changes, and smaller-scale floods have greater flood risk. This work can provide the scientific basis for hydrological modeling in complex conditions, hydrological responses to land use changes, the watershed flood control and disaster relief, and the watershed integrated management.