Investigating the distribution characteristics of earthquake disaster risks in the Sichuan–Yunnan region is of great importance for enhancing government emergency response capabilities and achieving sustainable regional development. This study, based on disaster systems theory, constructs a seismic risk evaluation index system for the Sichuan–Yunnan region and employs the entropy method to determine the comprehensive risk index for earthquake disasters across 37 prefecture-level cities. The findings reveal the following: (1) High-risk areas for disaster-causing factors are located in the Hengduan Mountain region and the North–South Mountain Range Valley Region; medium-risk areas are distributed along the northwestern edge of the Sichuan Basin; low-risk areas are situated in the eastern part of the Sichuan Basin and the Yunnan Plateau. (2) High-risk disaster-prone environments are found in the Hengduan Mountain region; medium-risk areas are present on the Yunnan Plateau and the western part of the North–South Mountain Range Valley Region; low-risk areas are in the Sichuan Basin. (3) High-vulnerability areas include the central Sichuan Basin and Kunming on the Yunnan Plateau; medium-vulnerability areas are located in the eastern and western parts of the Sichuan Basin; low-vulnerability areas are in the less developed parts of the Yunnan Plateau, the North–South Mountain Range Valley Region, and the Hengduan Mountain region. (4) High-risk seismic disaster areas are concentrated in the developed regions of the Sichuan Basin and the Yunnan Plateau; medium-risk areas are concentrated in the western part of the North–South Mountain Range Valley Region; low-risk areas are sporadically distributed in the eastern parts of the Sichuan–Yunnan region. (5) The vulnerability of the population, economy, and lifeline systems significantly explain the variation in seismic risk levels, all exceeding 0.70; the synergistic effects of disaster-causing factor danger, disaster-prone environment stability, and disaster-prone environment sensitivity are the most pronounced, with explanatory power exceeding 0.85 after factor interaction.
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