Abstract Based on the observation data of relative gravity and absolute gravity in southern Xinjiang since 2016, the dynamic change of regional gravity field in southern Xinjiang region and its relationship with the Jiashi MS6.4 earthquake on January 19, 2020 are systematically analyzed. The results show that: 1)The change of regional gravity field is closely related to regional tectonics, and many local gravity anomaly areas and high-gradient zones of gravity change are formed along Keping fault, implying that the fault activity caused significant changes of surface gravity field during 2016 to 2020. 2)The gravity field related to the preparation of the Jiashi earthquake has experienced evolution process of “positive gravity anomaly area—four quadrants distribution characteristic and high-gradient zone of gravity change along Keping fault—reverse change and earthquake occurrence”. 3)The cumulative change and differential change of gravity field all reflect the significant gravity anomaly changes before the Jiashi earthquake, which occurred in gradient zone of gravity change, the center of four quadrants, and near the turning of zero contour line. 4)The dynamic evolution of gravity field well reflects the medium-term precursor phenomenon during the preparation and occurrence of the Jiashi MS6.4 earthquake. Based on the anomaly changes of mobile gravity, a certain degree of medium-term prediction was made before the Jiashi MS6.4 earthquake, especially the location determination of strong earthquakes.