Electro-stream machining is mainly a process of electrochemical anode dissolution, which causes corrosion damage to the single-crystal material and affects the performance of the film holes under service conditions. Based on the microscopic analysis and in-situ fatigue test, the damage behavior of electro-stream machining on the film holes of DD6 single crystal superalloy were investigated. The results show that the corrosion zones of the film hole are all characteristics of electrolytic corrosion of DD6 single crystal superalloy, which a part of the γ phase is eroded and the γ′ phase is prominent. In addition, there are two ways of fatigue crack initiation of the DD6 single crystal superalloy specimen with a single hole: one is originate from the porous defect at the edge of the hole and the other is that from the electrolytic corrosion damage layer at the edge of the hole.