The correlation between flood loss rates, different indexes of influencing factors, and important degree of different indexes were quantitatively analyzed using the Spearman’s correlation coefficient and random forest methods. Flood loss rate functions for different provinces in middle and lower reaches of the Yangtze River(MLRYR)were constructed using exponential and power multiple regression functions, comprehensively considering the impacts of rainfall, disaster prevention and mitigation ability, socio-economic development, and natural resources on the flood disaster. By comparing the fitting results of the two functions, the optimal function was selected as the prediction model, and flood loss of different provinces in MLRYR during the period 2030-2100 under five shared socioeconomic pathways (SSPs) was estimated. The results show that the flood loss rates of different provinces in MLRYR are positively influenced by rainfall, and negatively influenced by socio-economic development, natural resources, and disaster prevention and mitigation ability. The constructed multiple regression function curves can well fit the variation of flood loss rates, especially, the function curves of economic loss rate and death rate for Jiangsu, Anhui, and Jiangxi provinces and Shanghai municipality have high fitting precision, and the determination coefficients are greater than 0.85. Under the rainfall scenarios of 1991 and 1998, the flood economic loss in MLRYR in the future shows an increasing trend compared with the historical losses, with the maximum increasing rates of 603% and 572%, respectively, and the flood-affected population in the future shows a decreasing trend, with the minimum decreasing rates of 72% and 52%, respectively. The flood economic loss and flood-affected population in MLRYR are the least, with decreasing trends under SSP4 that is characterized by adaptation challenges, the flood economic loss is the largest with an increasing trend under SSP5 that is dominated by economic development, and the flood-affected population is the largest with a trend to decrease and then increase under SSP3 that is characterized by regional rivalry. © 2023, Editorial Board of Water Resources Protection. All rights reserved.