The Xianshuihe fault zone is a seismo-genetic fault zone of left-lateral slip in Southwest China. Since 1725, a total of 59 Ms ≥ 5.0 earthquakes have occurred along this fault zone, including 18 Ms 6.0–6.9 and eight Ms ≥ 7.0 earthquakes. The seismic risk of the Xianshuihe fault zone is a large and realistic threat to the western Sichuan economic corridor. Based on previous studies, we carried out field geological survey and remote sensing interpretation in the fault zone. In addition, geophysical surveys, trenching and age-dating were conducted in the key parts to better understand the geometry, spatial distribution and activity of the fault zone. We infer to divide the fault zone into two parts: the northwest part and the southeast part, with total eight segments. Their Late Quaternary slip rates vary in a range of 11.5 mm/a – (3±1) mm/a. The seismic activities of the Xianshuihe fault zone are frequent and strong, periodical, and reoccurred. Combining the spatial and temporal distribution of the historical earthquakes, the seismic hazard of the Xianshuihe fault zone has been predicted by using the relationship between magnitude and frequency of earthquakes caused by different fault segments. The prediction results show that the segment between Daofu and Qianning has a possibility of Ms ≥ 7.0 earthquakes, while the segment between Shimian and Luding is likely to have earthquakes of about Ms 7.0. It is suggested to establish a GPS or InSAR-based real-time monitoring network of surface displacement to cover the Xianshuihe fault zone, and an early warning system of earthquakes and post seismic geohazards to cover the major residential areas.