750 kV grid as the main grid of Northwest China is now in rapid development period. On the basis of the characteristics of 750 kV transformer, the protection configuration and its related problems are analyzed. Considering that the differential protection of 750 kV transformer is quite perfect, the internal fault is mainly dependent on the differential protection to remove and the backup protection is primarily responsible for external faults at the bus and the local end of the adjacent lines. To meet the requirements for sensitivity and speed at external local faults without losing selectivity is the key issue for setting calculation in transformer backup protection. Based on the above analysis, the setting calculation method for 750 kV transformer protection is proposed and the applicability of impedance protection, improvement of differential protection, simplification of backup protection and automatic setting calculation of transformer protection are discussed as well. The scheme has been successfully applied to the 750 kV transformer protection in Northwest China.