To investigate the coupling relationship between ionospheric variations and great earthquakes in the seismic zone of southwest China, the total electron content (TEC) anomalies before Mw 6.0+ earthquakes in that area between 2001 and 2013 were analyzed to study the precursors of great earthquakes. To analyze the lithosphere-atmosphere-ionosphere effect, TEC estimated by the Center for Orbit Determination in Europe was used to determine anomalies prior to 18 moderate-to-great earthquakes with magnitudes of ≥ 6.0. Spatial and temporal TEC variations in the seismic zone were calculated and examined to study the relationship between the identified TEC anomalies and subsequent earthquakes. The results showed that ionospheric anomalies were observed before 72 % of earthquakes and among those anomalies, positive and negative anomalies accounted for approximately 58 % and 42 % of anomalies, respectively. Most of the ionospheric anomalies could be observed within 1 to 6 days prior to the earthquakes and approximately 82 % of ionospheric anomalies usually occurred between 13:00 and 18:00 in the region's local time. Furthermore, the anomaly amplitudes and occurrence time were proportional to the magnitude of the earthquake but the relationship was not linear. After eliminating the effect of solar activities and geomagnetic storms, some obvious and regular anomalous behavior in TEC could be detected on the 19th day before several earthquakes and the peak of anomaly enhancement coincided with the vertical projection of the epicenter. Our results indicate that these TEC anomalies may be the ionospheric precursors of forthcoming earthquakes in the seismic belt of southwest China.