A total three-dimensional method for calculating mixing loss is proposed in response to the problem that existing methods for evaluating the mixing loss of film cooling cannot accurately calculate the loss between mainstream and coolant in the area affected by passage secondary flow. Film holes with different compound angles are set in the suction surface based on HS1A turbine guide vane. Under the premise of meeting the requirements from film cooling effectiveness, the loss mechanism is analyzed by controlling the mainstream and coolant parameters. Different models are analyzed by using the entropy creation of mixing as the basis for loss evaluation. The results show that film cooling effectiveness is improved by arranging subregional compound angle holes with entropy creation of mixing increasing. And the loss of film deflection caused by passage secondary flow and film detachment can be reduced by setting compound angles.