Due to its excellent mechanical properties and good corrosion resistance at low to intermediate temperatures, nickel-based alloy N06625 has gradually become an ideal material for high-temperature gas-cooled reactor evaporators in nuclear power plants. It is currently receiving more and more attention. In this work, the tensile test of nickel-based alloy N06625 was carried out at room temperature to 900℃. The dynamic strain aging (DSA) process and microstructure evolution were studied by electron back-scatter diffraction (EBSD). The dynamic strain aging and intermediate temperature embrittlement of nickel-based alloy N06625 in the temperature range 25–900℃ were systematically studied. The results show that the stress-strain curve exhibits a serrated shape at 200–700℃, and with the increase in temperature, the serrated type changes from type A to type A+B and type C. The type A and type (A+B) serrations are related to the diffusion of interstitial carbon atoms. The interaction between substitutional elements Cr and Mo and movable dislocations causes the type C serration. As the temperature increases, high-density dislocations accumulate at the grain boundaries, and the proportion of substructural grains increases. A brittle fracture occurs at 600–800℃. The fracture mechanism may be due to the stress concentration at the grain boundary caused by the appearance of micropore, which weakens the grain boundary's strength and promotes the grain boundary's early failure. The continuous increase of strain makes the micropore fuse and grow to form a crack source.