Based on least-square technique, this paper presents a method to derive GPS-TEC and instrumental biases of GPS observation in equatorial anomaly region. Applying the method to the data from 4 GPS receivers located at Fuzhou, Xiamen, Guangzhou and Nanning in 2006, the TEC is obtained for 48 meshes with size of 3°× 1° in longitude and latitude covering an area of 20~28°N, 105°~123 °E. The instrumental biases are stable in the whole year. The satellite biases are close to those published by Center for Orbit Determination in Europe. This method can be used to study the ionosphere in equatorial anomaly region.