<p>The Sichuan-Yunnan region is located on the southeastern edge of the Tibetan Plateau. The region has long been characterized by frequent and intense seismic activity. Small and medium-sized earthquakes are found almost everywhere in the region, making it one of the most seismically active areas in mainland China. We have established a multi-dimensional monitoring and evaluation system based on long-term geological data, seismic data, geodetic data, etc. We combine underground activities with surface monitoring data and are constrained by high-density observation data from the Global Navigation Satellite System (GNSS) autonomous network construction. Finally, based on the factor analysis method, the weights of evaluation indicators are established, and a crustal stability evaluation model is constructed using the multi-factor weighted superposition method to quantitatively evaluate the crustal stability of the Sichuan Yunnan region. The evaluation results show that the Sichuan-Yunnan area is mainly a relatively unstable and unstable region, accounting for 50.32% of the total area of the total area. The level of east–west stability is obvious, and the stability of the west-to-east has gradually increased. Among them, the unstable zone is mainly located in Xianshuihe district, Longmenshan district, Anning river-Daliangshan-Xiaojiang district, Jinsha river-Longpan Qiaohou-Red River district. Overall, the Y-shaped structure zone has the worst crustal stability near the Y-shaped structure belt. The west is second and the east is the best. This evaluation is of great significance for urban construction, engineering development planning, major engineering site selection, and safety evaluation in the Sichuan-Yunnan region. The construction site provides scientific support.</p> Graphical Abstract <p></p>