The co-seismic response of underground fluid wells to the 2015 Nepal M_S8.1earthquake and its aftershock M_S7.5 in the Yunnan area were recorded. Based on observed data, this paper analyzes the spatial distribution, anomaly shape, anomaly amplitude, and anomaly start and end times in the appropriate wells. The results show that the co-seismic responses were mainly concentrated in the southeast of the Sichuan-Yunnan rhombic block, the east of the Yunnan-Myanmar arc block, and the west of Yunnan area. The anomaly shapes of the co-seismic responses of water level and temperature in the same well are complicated and multiple. The observation items in a single well show consistency and are unconnected to earthquake magnitude, epicenter distance, and azimuth. The well's ability to record earthquakes is connected to the resolution of the observation instrument, well aquifer condition, and so on. The co-seismic response anomaly amplitude shows a certain quantitative relationship with magnitude and epicenter distance. In recent years, seismic activity has shown a "quiet-active-quiet" characteristic and small earthquakes have been clustered in the Yunnan area. In the near future, there is a risk of moderate-strong earthquakes in the west-northwest and southwest of Yunnan.